{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:02:46Z","timestamp":1792648966511,"version":"4.5.0"},"reference-count":277,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T00:00:00Z","timestamp":1495152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Cardiac fibrosis, the excessive accumulation of extracellular matrix (ECM), remains an unresolved problem in most forms of heart disease. In order to be successful in preventing, attenuating or reversing cardiac fibrosis, it is essential to understand the processes leading to ECM production and accumulation. Cardiac fibroblasts are the main producers of cardiac ECM, and harbor great phenotypic plasticity. They are activated by the disease-associated changes in mechanical properties of the heart, including stretch and increased tissue stiffness. Despite much remaining unknown, an interesting body of evidence exists on how mechanical forces are translated into transcriptional responses important for determination of fibroblast phenotype and production of ECM constituents. Such mechanotransduction can occur at multiple cellular locations including the plasma membrane, cytoskeleton and nucleus. Moreover, the ECM functions as a reservoir of pro-fibrotic signaling molecules that can be released upon mechanical stress. We here review the current status of knowledge of mechanotransduction signaling pathways in cardiac fibroblasts that culminate in pro-fibrotic gene expression.<\/jats:p>","DOI":"10.3390\/jcm6050053","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T01:47:33Z","timestamp":1495504053000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":175,"title":["The Soft- and Hard-Heartedness of Cardiac Fibroblasts: Mechanotransduction Signaling Pathways in Fibrosis of the Heart"],"prefix":"10.3390","volume":"6","author":[{"given":"Kate","family":"Herum","sequence":"first","affiliation":[{"name":"Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"},{"name":"Center for Heart Failure Research, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Lunde","sequence":"additional","affiliation":[{"name":"Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"},{"name":"Center for Heart Failure Research, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"McCulloch","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geir","family":"Christensen","sequence":"additional","affiliation":[{"name":"Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"},{"name":"Center for Heart Failure Research, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/ejhf.696","article-title":"Myocardial fibrosis: Biomedical research from bench to bedside","volume":"19","author":"Gyongyosi","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1189\/jlb.72.4.752","article-title":"Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation","volume":"72","author":"Weber","year":"2002","journal-title":"J. Leukoc. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0022-2828(89)90778-5","article-title":"Patterns of myocardial fibrosis","volume":"21","author":"Weber","year":"1989","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrcardio.2012.158","article-title":"Myofibroblast-mediated mechanisms of pathological remodelling of the heart","volume":"10","author":"Weber","year":"2013","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s10741-012-9365-4","article-title":"Fibrosis and heart failure","volume":"19","author":"Segura","year":"2014","journal-title":"Heart Fail. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1146\/annurev.biochem.77.032207.120833","article-title":"Collagen structure and stability","volume":"78","author":"Shoulders","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cardiores.2004.06.006","article-title":"Matricellular proteins in the heart: Possible role during stress and remodeling","volume":"64","author":"Schellings","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1161\/CIRCRESAHA.114.302533","article-title":"Myocardial extracellular matrix: An ever-changing and diverse entity","volume":"114","author":"Rienks","year":"2014","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s00059-012-3719-5","article-title":"Diastolic heart failure: What we still don\u2019t know. Looking for new concepts, diagnostic approaches, and the role of comorbidities","volume":"37","author":"Tschope","year":"2012","journal-title":"Herz"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrcardio.2009.199","article-title":"Myocardial remodeling after infarction: The role of myofibroblasts","volume":"7","author":"Diez","year":"2010","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cardiores.2004.08.020","article-title":"Structural and functional characterisation of cardiac fibroblasts","volume":"65","author":"Camelliti","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.yjmcc.2013.11.003","article-title":"Origin, development, and differentiation of cardiac fibroblasts","volume":"70","author":"Lajiness","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lindner, D., Zietsch, C., Becher, P.M., Schulze, K., Schultheiss, H.P., Tschope, C., and Westermann, D. (2012). Differential expression of matrix metalloproteases in human fibroblasts with different origins. Biochem. Res. Int.","DOI":"10.1155\/2012\/875742"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1253\/circj.CJ-16-1003","article-title":"Defining the cardiac fibroblast","volume":"80","author":"Ivey","year":"2016","journal-title":"Circ. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/ejhf.312","article-title":"Searching for new mechanisms of myocardial fibrosis with diagnostic and\/or therapeutic potential","volume":"17","author":"Heymans","year":"2015","journal-title":"Eur. J. Heart Fail."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3109\/03008207.2014.904856","article-title":"Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor \u03b2","volume":"55","author":"Watson","year":"2014","journal-title":"Connect. Tissue Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.cardiores.2004.04.030","article-title":"TGF-\u03b21 and angiotensin networking in cardiac remodeling","volume":"63","author":"Rosenkranz","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/eurheartj\/16.suppl_C.45","article-title":"Hormonal regulation of cardiac fibroblast function","volume":"16","author":"Brilla","year":"1995","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1161\/CIRCRESAHA.116.302317","article-title":"Innate immunity and the failing heart: The cytokine hypothesis revisited","volume":"116","author":"Mann","year":"2015","journal-title":"Circ. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3109\/10409238.2015.1033511","article-title":"Advances in toll-like receptor biology: Modes of activation by diverse stimuli","volume":"50","author":"Bryant","year":"2015","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jcp.2012.09.015","article-title":"Patient-specific models of cardiac biomechanics","volume":"244","author":"Krishnamurthy","year":"2013","journal-title":"J. Comput. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.jacc.2005.10.040","article-title":"Noninvasive myocardial strain measurement by speckle tracking echocardiography: Validation against sonomicrometry and tagged magnetic resonance imaging","volume":"47","author":"Amundsen","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.media.2005.01.003","article-title":"Tagged magnetic resonance imaging of the heart: A survey","volume":"9","author":"Axel","year":"2005","journal-title":"Med. Image Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.yjmcc.2015.11.025","article-title":"Mechanical control of cardiac myofibroblasts","volume":"93","author":"Shafieyan","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1083\/jcb.200506179","article-title":"Focal adhesion size controls tension-dependent recruitment of \u03b1-smooth muscle actin to stress fibers","volume":"172","author":"Goffin","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1038\/ncomms7333","article-title":"Cyclic stretching of soft substrates induces spreading and growth","volume":"6","author":"Cui","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13661","DOI":"10.1073\/pnas.94.25.13661","article-title":"Cell locomotion and focal adhesions are regulated by substrate flexibility","volume":"94","author":"Pelham","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1089\/107632703322066705","article-title":"Cell-matrix adhesions on poly(vinyl alcohol) hydrogels","volume":"9","author":"Zajaczkowski","year":"2003","journal-title":"Tissue Eng."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1242\/jcs.029678","article-title":"Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: Scar-like rigidity inhibits beating","volume":"121","author":"Engler","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"H2196","DOI":"10.1152\/ajpheart.01017.2005","article-title":"Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance","volume":"290","author":"Berry","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.1529\/biophysj.106.101386","article-title":"Fibroblast adaptation and stiffness matching to soft elastic substrates","volume":"93","author":"Solon","year":"2007","journal-title":"Biophys. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"L25","DOI":"10.1016\/j.bpj.2010.12.3744","article-title":"Cell shape and substrate rigidity both regulate cell stiffness","volume":"100","author":"Tee","year":"2011","journal-title":"Biophys. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1016\/j.biomaterials.2004.08.009","article-title":"Evaluation of polydimethylsiloxane scaffolds with physiologically-relevant elastic moduli: Interplay of substrate mechanics and surface chemistry effects on vascular smooth muscle cell response","volume":"26","author":"Brown","year":"2005","journal-title":"Biomaterials"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Caliari, S.R., Perepelyuk, M., Cosgrove, B.D., Tsai, S.J., Lee, G.Y., Mauck, R.L., Wells, R.G., and Burdick, J.A. (2016). Stiffening hydrogels for investigating the dynamics of hepatic stellate cell mechanotransduction during myofibroblast activation. Sci. Rep., 6.","DOI":"10.1038\/srep21387"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"0210031","DOI":"10.1115\/1.4032429","article-title":"Mechanical characterization of a dynamic and tunable methacrylated hyaluronic acid hydrogel","volume":"138","author":"Ondeck","year":"2016","journal-title":"J. Biomech. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1039\/C6IB00027D","article-title":"Gradually softening hydrogels for modeling hepatic stellate cell behavior during fibrosis regression","volume":"8","author":"Caliari","year":"2016","journal-title":"Integr. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Throm Quinlan, A.M., Sierad, L.N., Capulli, A.K., Firstenberg, L.E., and Billiar, K.L. (2011). Combining dynamic stretch and tunable stiffness to probe cell mechanobiology in vitro. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023272"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Herum, K.M., Choppe, J., Kumar, A., Engler, A.J., and McCulloch, A.D. (2017). Mechanical regulation of cardiac fibroblast pro-fibrotic phenotypes. Mol. Biol. Cell.","DOI":"10.1091\/mbc.e17-01-0014"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/HYPERTENSIONAHA.112.196113","article-title":"Collagen cross-linking but not collagen amount associates with elevated filling pressures in hypertensive patients with stage c heart failure: Potential role of lysyl oxidase","volume":"60","author":"Lopez","year":"2012","journal-title":"Hypertension"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jacc.2010.10.024","article-title":"Diastolic tissue doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction","volume":"57","author":"Kasner","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"H1277","DOI":"10.1152\/ajpheart.00168.2002","article-title":"Glycated collagen cross-linking alters cardiac mechanics in volume-overload hypertrophy","volume":"284","author":"Herrmann","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"C606","DOI":"10.1152\/ajpcell.00269.2001","article-title":"Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells","volume":"282","author":"Wang","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1242\/dev.024166","article-title":"Mechanical control of tissue and organ development","volume":"137","author":"Mammoto","year":"2010","journal-title":"Development"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1161\/01.RES.77.1.182","article-title":"Transverse shear along myocardial cleavage planes provides a mechanism for normal systolic wall thickening","volume":"77","author":"LeGrice","year":"1995","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.2353\/ajpath.2007.070112","article-title":"The myofibroblast: One function, multiple origins","volume":"170","author":"Hinz","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/sj.jid.5700613","article-title":"Formation and function of the myofibroblast during tissue repair","volume":"127","author":"Hinz","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.yjmcc.2015.11.017","article-title":"The janus face of myofibroblasts in the remodeling heart","volume":"91","author":"Hermans","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm809","article-title":"Myofibroblasts and mechano-regulation of connective tissue remodelling","volume":"3","author":"Tomasek","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.yjmcc.2014.02.017","article-title":"Cardiac fibroblast in development and wound healing","volume":"70","author":"Deb","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.stem.2016.10.005","article-title":"Cardiac fibroblasts adopt osteogenic fates and can be targeted to attenuate pathological heart calcification","volume":"20","author":"Pillai","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yjmcc.2015.12.031","article-title":"Origins of cardiac fibroblasts","volume":"91","author":"Cattaneo","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nm1613","article-title":"Endothelial-to-mesenchymal transition contributes to cardiac fibrosis","volume":"13","author":"Zeisberg","year":"2007","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/path.2281","article-title":"Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction","volume":"214","author":"Popa","year":"2008","journal-title":"J. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/CIRCULATIONAHA.106.650903","article-title":"Bone marrow derived cells are involved in the pathogenesis of cardiac hypertrophy in response to pressure overload","volume":"116","author":"Endo","year":"2007","journal-title":"Circulation"},{"key":"ref_56","first-page":"909","article-title":"Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche","volume":"24","author":"Gutierrez","year":"2009","journal-title":"Histol Histopathol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kanisicak, O., Khalil, H., Ivey, M.J., Karch, J., Maliken, B.D., Correll, R.N., Brody, M.J., Lin, S.-C.J., Aronow, B.J., and Tallquist, M.D. (2016). Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat. Commun., 7.","DOI":"10.1038\/ncomms12260"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Tallquist, M.D., and Molkentin, J.D. (2017). Redefining the identity of cardiac fibroblasts. Nat. Rev. Cardiol.","DOI":"10.1038\/nrcardio.2017.57"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1083\/jcb.142.3.873","article-title":"The fibronectin domain ed-a is crucial for myofibroblastic phenotype induction by transforming growth factor-\u03b21","volume":"142","author":"Serini","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/nm.3282","article-title":"Targeting of \u03b1v integrin identifies a core molecular pathway that regulates fibrosis in several organs","volume":"19","author":"Henderson","year":"2013","journal-title":"Nat. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1161\/CIRCRESAHA.116.308643","article-title":"Targeted ablation of periostin-expressing activated fibroblasts prevents adverse cardiac remodeling in mice","volume":"118","author":"Kaur","year":"2016","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1006\/jmcc.1999.1017","article-title":"Differential responses of adult cardiac fibroblasts to in vitro biaxial strain patterns","volume":"31","author":"Lee","year":"1999","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Turner, N.A., and Porter, K.E. (2013). Function and fate of myofibroblasts after myocardial infarction. Fibrogenesis Tissue Repair, 6.","DOI":"10.1186\/1755-1536-6-5"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1161\/CIRCRESAHA.116.309916","article-title":"Crossing into the next frontier of cardiac extracellular matrix research","volume":"119","author":"Spinale","year":"2016","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"12001","DOI":"10.1074\/jbc.R300038200","article-title":"Integrins in mechanotransduction","volume":"279","author":"Katsumi","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1152\/physrev.00008.2011","article-title":"Matricellular proteins in cardiac adaptation and disease","volume":"92","author":"Frangogiannis","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.matbio.2015.05.006","article-title":"The extracellular matrix and transforming growth factor-\u03b21: Tale of a strained relationship","volume":"47","author":"Hinz","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/cvr\/cvu053","article-title":"Integrins \u03b1v\u03b25 and \u03b1v\u03b23 promote latent TGF-\u03b21 activation by human cardiac fibroblast contraction","volume":"102","author":"Sarrazy","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ejcb.2008.01.012","article-title":"Integrins and the activation of latent transforming growth factor \u03b21\u2014An intimate relationship","volume":"87","author":"Wipff","year":"2008","journal-title":"Eur. J. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/nm.3421","article-title":"It has to be the \u03b1v: Myofibroblast integrins activate latent TGF-\u03b21","volume":"19","author":"Hinz","year":"2013","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.yjmcc.2013.11.015","article-title":"Fibroblasts in myocardial infarction: A role in inflammation and repair","volume":"70","author":"Shinde","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kelsh, R., You, R., Horzempa, C., Zheng, M., and McKeown-Longo, P.J. (2014). Regulation of the innate immune response by fibronectin: Synergism between the iii-1 and eda domains. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102974"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3109\/08977194.2011.595714","article-title":"TGF-\u03b2 signaling in fibrosis","volume":"29","author":"Biernacka","year":"2011","journal-title":"Growth Factors"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.yjmcc.2010.10.033","article-title":"Transforming growth factor TGF-\u03b2 signaling in cardiac remodeling","volume":"51","author":"Dobaczewski","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.biocel.2007.11.026","article-title":"The role of proteases in transforming growth factor-\u03b2 activation","volume":"40","author":"Jenkins","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1002\/jcp.24094","article-title":"Specificity of latent TGF-\u03b2 binding protein (LTBP) incorporation into matrix: Role of fibrillins and fibronectin","volume":"227","author":"Zilberberg","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.matbio.2015.05.005","article-title":"Latent TGF-\u03b2-binding proteins","volume":"47","author":"Robertson","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.2353\/ajpath.2009.090393","article-title":"Integrin-mediated transforming growth factor-\u03b2 activation, a potential therapeutic target in fibrogenic disorders","volume":"175","author":"Nishimura","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1083\/jcb.200704042","article-title":"Myofibroblast contraction activates latent TGF-\u03b21 from the extracellular matrix","volume":"179","author":"Wipff","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.yexcr.2012.01.020","article-title":"Epithelial cells utilize cortical actin\/myosin to activate latent TGF-\u03b2 through integrin \u03b1v\u03b26-dependent physical force","volume":"318","author":"Giacomini","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1083\/jcb.201402006","article-title":"Prestress in the extracellular matrix sensitizes latent TGF-\u03b21 for activation","volume":"207","author":"Klingberg","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.cub.2011.04.007","article-title":"Conversion of mechanical force into TGF-\u03b2-mediated biochemical signals","volume":"21","author":"Maeda","year":"2011","journal-title":"Curr. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/cvr\/cvt100","article-title":"Osteopontin-mediated myocardial fibrosis in heart failure: A role for lysyl oxidase?","volume":"99","author":"Lopez","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Yang, J., Savvatis, K., Kang, J.S., Fan, P., Zhong, H., Schwartz, K., Barry, V., Mikels-Vigdal, A., Karpinski, S., and Kornyeyev, D. (2016). Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment. Nat. Commun., 7.","DOI":"10.1038\/ncomms13710"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1159\/000354222","article-title":"Activation of extracellular transglutaminase 2 by mechanical force in the arterial wall","volume":"50","author":"Belkin","year":"2013","journal-title":"J. Vasc. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"18411","DOI":"10.1074\/jbc.M109.012948","article-title":"Heparan sulfate proteoglycans are receptors for the cell-surface trafficking and biological activity of transglutaminase-2","volume":"284","author":"Scarpellini","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1681\/ASN.2013050563","article-title":"Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis","volume":"25","author":"Scarpellini","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"13063","DOI":"10.1074\/jbc.M111.294819","article-title":"Characterization of heparin-binding site of tissue transglutaminase: Its importance in cell surface targeting, matrix deposition, and cell signaling","volume":"287","author":"Wang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/cvr\/cvv002","article-title":"Syndecan-4 is a key determinant of collagen cross-linking and passive myocardial stiffness in the pressure-overloaded heart","volume":"106","author":"Herum","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1139\/cjpp-2015-0019","article-title":"Osteopontin is proteolytically processed by matrix metalloproteinase 9","volume":"93","author":"Lindsey","year":"2015","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.bbamem.2003.09.006","article-title":"Interaction of rantes with syndecan-1 and syndecan-4 expressed by human primary macrophages","volume":"1617","author":"Slimani","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1021\/bi00430a047","article-title":"Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules","volume":"28","author":"Bashkin","year":"1989","journal-title":"Biochemistry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ijcard.2012.04.047","article-title":"Increased circulating mitochondrial DNA after myocardial infarction","volume":"158","author":"Bliksoen","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial damps cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"31332","DOI":"10.1074\/jbc.M103217200","article-title":"Endocytosed hsp60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll\/interleukin-1 receptor signaling pathway in innate immune cells","volume":"276","author":"Vabulas","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.4049\/jimmunol.175.5.2777","article-title":"Heat shock proteins as endogenous adjuvants in sterile and septic inflammation","volume":"175","author":"Quintana","year":"2005","journal-title":"J. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nri2873","article-title":"Sterile inflammation: Sensing and reacting to damage","volume":"10","author":"Chen","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/ni1457","article-title":"Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by hmgb1 and rage","volume":"8","author":"Tian","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1074\/jbc.M306793200","article-title":"Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein","volume":"279","author":"Park","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.matbio.2013.03.008","article-title":"Combined effects of interleukin-1\u03b1 and transforming growth factor-\u03b21 on modulation of human cardiac fibroblast function","volume":"32","author":"Hemmings","year":"2013","journal-title":"Matrix Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vph.2013.06.002","article-title":"Effects of interleukin-1 on cardiac fibroblast function: Relevance to post-myocardial infarction remodelling","volume":"60","author":"Turner","year":"2014","journal-title":"Vascul. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4330\/wjc.v8.i5.340","article-title":"Tenascin c upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4","volume":"8","author":"Maqbool","year":"2016","journal-title":"World J. Cardiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1111\/febs.12145","article-title":"Biological interplay between proteoglycans and their innate immune receptors in inflammation","volume":"280","author":"Frey","year":"2013","journal-title":"FEBS J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1111\/febs.12235","article-title":"Lumican is increased in experimental and clinical heart failure, and its production by cardiac fibroblasts is induced by mechanical and proinflammatory stimuli","volume":"280","author":"Engebretsen","year":"2013","journal-title":"FEBS J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1152\/japplphysiol.00793.2012","article-title":"Decorin, lumican, and their gag chain-synthesizing enzymes are regulated in myocardial remodeling and reverse remodeling in the mouse","volume":"114","author":"Engebretsen","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.yjmcc.2015.10.003","article-title":"Shedding of syndecan-4 promotes immune cell recruitment and mitigates cardiac dysfunction after lipopolysaccharide challenge in mice","volume":"88","author":"Strand","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"17079","DOI":"10.1074\/jbc.M310859200","article-title":"Hyaluronan fragments stimulate endothelial recognition of injury through TLR4","volume":"279","author":"Taylor","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.4049\/jimmunol.177.2.1272","article-title":"Hyaluronan fragments act as an endogenous danger signal by engaging TLR2","volume":"177","author":"Scheibner","year":"2006","journal-title":"J. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00441-016-2454-2","article-title":"Syndecans in heart fibrosis","volume":"365","author":"Lunde","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1152\/japplphysiol.01350.2011","article-title":"Chemokines regulate small leucine-rich proteoglycans in the extracellular matrix of the pressure-overloaded right ventricle","volume":"112","author":"Waehre","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1111\/febs.12161","article-title":"Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan-4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure-overloaded heart","volume":"280","author":"Strand","year":"2013","journal-title":"FEBS J."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Melleby, A.O., Strand, M.E., Romaine, A., Herum, K.M., Skrbic, B., Dahl, C.P., Sjaastad, I., Fiane, A.E., Filmus, J., and Christensen, G. (2016). The heparan sulfate proteoglycan glypican-6 is upregulated in the failing heart, and regulates cardiomyocyte growth through ERK1\/2 signaling. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165079"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.tcb.2015.02.008","article-title":"Emerging properties of adhesion complexes: What are they and what do they do?","volume":"25","author":"Humphries","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1242\/jcs.162891","article-title":"Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease","volume":"128","author":"Schroer","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","article-title":"Integrins: Bidirectional, allosteric signaling machines","volume":"110","author":"Hynes","year":"2002","journal-title":"Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1242\/jcs.018093","article-title":"Integrin signalling at a glance","volume":"122","author":"Harburger","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/ncb0807-858","article-title":"Functional atlas of the integrin adhesome","volume":"9","author":"Itzkovitz","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Teoh, C.M., Tam, J.K., and Tran, T. (2012). Integrin and gpcr crosstalk in the regulation of ASM contraction signaling in asthma. J. Allergy, 2012.","DOI":"10.1155\/2012\/341282"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/embor.2009.276","article-title":"Integrin-TGF-\u03b2 crosstalk in fibrosis, cancer and wound healing","volume":"11","author":"Margadant","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"18066","DOI":"10.1074\/jbc.M801213200","article-title":"Direct binding of integrin \u03b1v\u03b23 to FGF1 plays a role in FGF1 signaling","volume":"283","author":"Mori","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Agarwal, S.K. (2014). Integrins and cadherins as therapeutic targets in fibrosis. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00131"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1530\/JOE-10-0377","article-title":"Extracellular matrix and cell signalling: The dynamic cooperation of integrin, proteoglycan and growth factor receptor","volume":"209","author":"Kim","year":"2011","journal-title":"J. Endocrinol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1172\/JCI1026","article-title":"Extracellular signal-regulated kinase and c-Jun NH2-terminal kinase activation by mechanical stretch is integrin-dependent and matrix-specific in rat cardiac fibroblasts","volume":"101","author":"MacKenna","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.yjmcc.2015.11.010","article-title":"Integrins and integrin-related proteins in cardiac fibrosis","volume":"93","author":"Chen","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1111\/j.1582-4934.2008.00638.x","article-title":"Integrin \u03b11\u03b21 is involved in the differentiation into myofibroblasts in adult reactive tissues in vivo","volume":"13","author":"Rodriguez","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_126","first-page":"213","article-title":"Epithelial cell \u03b13\u03b21 integrin links \u03b2-catenin and smad signaling to promote myofibroblast formation and pulmonary fibrosis","volume":"119","author":"Kim","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"40212","DOI":"10.1074\/jbc.M110.123703","article-title":"RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4\/2 \u03b15\u03b21 integrin co-signaling","volume":"285","author":"Wang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.yjmcc.2003.11.007","article-title":"\u03b18\u03b21 integrin is upregulated in myofibroblasts of fibrotic and scarring myocardium","volume":"36","author":"Bouzeghrane","year":"2004","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1242\/bio.011825","article-title":"Matrix compliance and the regulation of cytokinesis","volume":"4","author":"Sambandamoorthy","year":"2015","journal-title":"Biol. Open"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jdermsci.2006.09.012","article-title":"Crucial role of fibroblast integrins \u03b12 and \u03b21 in maintaining the structural and mechanical properties of the skin","volume":"45","author":"Fujimura","year":"2007","journal-title":"J. Dermatol. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/jid.2012.438","article-title":"Integrin \u03b21 is required for dermal homeostasis","volume":"133","author":"Liu","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"13548","DOI":"10.1074\/jbc.270.22.13548","article-title":"Integrin \u03b12\u03b21 is a positive regulator of collagenase (MMP-1) and collagen \u03b11(I) gene expression","volume":"270","author":"Riikonen","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.matbio.2014.09.001","article-title":"Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on mmp expression and extracellular matrix remodeling by fibroblasts","volume":"40","author":"Zhang","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Balasubramanian, S., Quinones, L., Kasiganesan, H., Zhang, Y., Pleasant, D.L., Sundararaj, K.P., Zile, M.R., Bradshaw, A.D., and Kuppuswamy, D. (2012). \u03b23 Integrin in cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouse. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045076"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1097\/RLU.0000000000000426","article-title":"Is the change of integrin \u03b1v\u03b23 expression in the infarcted myocardium related to the clinical outcome?","volume":"39","author":"Luo","year":"2014","journal-title":"Clin Nucl Med"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"16245","DOI":"10.1073\/pnas.0902818106","article-title":"Clustering of \u03b15\u03b21 integrins determines adhesion strength whereas \u03b1v\u03b23 and talin enable mechanotransduction","volume":"106","author":"Gauthier","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1006\/dbio.2001.0363","article-title":"Alpha11\u03b21 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells","volume":"237","author":"Tiger","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.matbio.2009.11.003","article-title":"The human \u03b111 integrin promoter drives fibroblast-restricted expression in vivo and is regulated by TGF-\u03b21 in a smad- and sp1-dependent manner","volume":"29","author":"Lu","year":"2010","journal-title":"Matrix Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/cvr\/cvs259","article-title":"Alpha11 integrin stimulates myofibroblast differentiation in diabetic cardiomyopathy","volume":"96","author":"Connelly","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1038\/jid.2015.24","article-title":"Reduced granulation tissue and wound strength in the absence of \u03b111\u03b21 integrin","volume":"135","author":"Schulz","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"10434","DOI":"10.1074\/jbc.M109.078766","article-title":"The fibroblast integrin \u03b111\u03b21 is induced in a mechanosensitive manner involving activin a and regulates myofibroblast differentiation","volume":"285","author":"Carracedo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1242\/jcs.188672","article-title":"The integrin-collagen connection\u2014A glue for tissue repair?","volume":"129","author":"Zeltz","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/jcp.24708","article-title":"Glycated collagen induces \u03b111 integrin expression through TGF-\u03b22 and smad3","volume":"230","author":"Arora","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/00004872-200301000-00002","article-title":"Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes","volume":"21","author":"Aronson","year":"2003","journal-title":"J. Hypertens."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1038\/onc.2015.254","article-title":"Integrin \u03b111\u03b21 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non-small cell lung cancer","volume":"35","author":"Navab","year":"2016","journal-title":"Oncogene"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"H96","DOI":"10.1152\/ajpheart.00918.2015","article-title":"The \u03b111 integrin mediates fibroblast-extracellular matrix-cardiomyocyte interactions in health and disease","volume":"311","author":"Civitarese","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0962-8924(97)01172-0","article-title":"Integrin signalling and tyrosine phosphorylation: Just the faks?","volume":"8","author":"Schlaepfer","year":"1998","journal-title":"Trends Cell Biol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev.biophys.050708.133744","article-title":"Biochemical and structural properties of the integrin-associated cytoskeletal protein talin","volume":"38","author":"Critchley","year":"2009","journal-title":"Annu. Rev. Biophys."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1074\/jbc.M112.427484","article-title":"Talin1 has unique expression versus talin 2 in the heart and modifies the hypertrophic response to pressure overload","volume":"288","author":"Manso","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/ncb3336","article-title":"Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity","volume":"18","author":"Oria","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"14805","DOI":"10.1074\/jbc.M112.435271","article-title":"Regulation of matrix assembly through rigidity-dependent fibronectin conformational changes","volume":"288","author":"Carraher","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"19372","DOI":"10.1073\/pnas.1307405110","article-title":"Distinct biophysical mechanisms of focal adhesion kinase mechanoactivation by different extracellular matrix proteins","volume":"110","author":"Seong","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.yjmcc.2013.10.019","article-title":"Myofibroblasts: Trust your heart and let fate decide","volume":"70","author":"Davis","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.yjmcc.2015.12.016","article-title":"Transcriptional control of cardiac fibroblast plasticity","volume":"91","author":"Lighthouse","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Molkentin, J.D., Bugg, D., Ghearing, N., Dorn, L.E., Kim, P., Sargent, M.A., Gunaje, J., Otsu, K., and Davis, J.M. (2017). Fibroblast-specific genetic manipulation of p38 MAPK in vivo reveals its central regulatory role in fibrosis. Circulation.","DOI":"10.1161\/CIRCULATIONAHA.116.026238"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrm1587","article-title":"Gef means go: Turning on Rho GTPases with guanine nucleotide-exchange factors","volume":"6","author":"Rossman","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ncb2254","article-title":"The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins","volume":"13","author":"Guilluy","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1253\/circj.CJ-16-0433","article-title":"Rho kinases and cardiac remodeling","volume":"80","author":"Shimizu","year":"2016","journal-title":"Circ. J."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Zhang, J., Fan, G., Zhao, H., Wang, Z., Li, F., Zhang, P., Zhang, J., Wang, X., and Wang, W. (2017). Targeted inhibition of focal adhesion kinase attenuates cardiac fibrosis and preserves heart function in adverse cardiac remodeling. Sci. Rep., 7.","DOI":"10.1038\/srep43146"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1242\/jcs.02970","article-title":"Syndecan-1 regulates \u03b1v\u03b25 integrin activity in b82l fibroblasts","volume":"119","author":"McQuade","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1016\/j.yexcr.2007.08.002","article-title":"Syndecans promote integrin-mediated adhesion of mesenchymal cells in two distinct pathways","volume":"313","author":"Whiteford","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1161\/01.HYP.35.1.273","article-title":"Angiotensin II enhances integrin and \u03b1-actinin expression in adult rat cardiac fibroblasts","volume":"35","author":"Kawano","year":"2000","journal-title":"Hypertension"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev-cellbio-100109-104126","article-title":"Transmembrane signaling proteoglycans","volume":"26","author":"Couchman","year":"2010","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1161\/hq0102.100314","article-title":"Mechanical stress regulates syndecan-4 expression and redistribution in vascular smooth muscle cells","volume":"22","author":"Li","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"7617","DOI":"10.1074\/jbc.M207123200","article-title":"Syndecan-4 associates with \u03b1-actinin","volume":"278","author":"Greene","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1152\/physiolgenomics.00144.2002","article-title":"Increased syndecan expression following myocardial infarction indicates a role in cardiac remodeling","volume":"16","author":"Finsen","year":"2004","journal-title":"Physiol. Genom."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrm2289","article-title":"Synergistic control of cell adhesion by integrins and syndecans","volume":"8","author":"Morgan","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"22102","DOI":"10.1073\/pnas.0902639106","article-title":"Defining the role of Syndecan-4 in mechanotransduction using surface-modification approaches","volume":"106","author":"Bellin","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.yjmcc.2012.11.006","article-title":"Syndecan-4 signaling via nfat regulates extracellular matrix production and cardiac myofibroblast differentiation in response to mechanical stress","volume":"54","author":"Herum","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Cavalheiro, R.P., Lima, M.A., Jarrouge-Boucas, T.R., Viana, G.M., Lopes, C.C., Coulson-Thomas, V.J., Dreyfuss, J.L., Yates, E.A., Tersariol, I.L., and Nader, H.B. (2017). Coupling of vinculin to F-actin demands syndecan-4 proteoglycan. Matrix Biol.","DOI":"10.1016\/j.matbio.2016.12.006"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Finsen, A.V., Lunde, I.G., Sjaastad, I., \u00d8stli, E.K., Lyngra, M., Jarstadmarken, H.O., Hasic, A., Nyg\u00e5rd, S., Wilcox-Adelman, S.A., and Goetinck, P.F. (2011). Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028302"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.yjmcc.2012.12.008","article-title":"Syndecan-4: A component of the mechanosensory apparatus of cardiac fibroblasts","volume":"56","author":"Samarel","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1083\/jcb.201501060","article-title":"Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels","volume":"210","author":"Gopal","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1016\/j.bbamcr.2015.07.011","article-title":"Syndecan-4 ectodomain evokes mobilization of podocyte TRPC6 channels and their associated pathways: An essential role for integrin signaling","volume":"1853","author":"Kim","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.devcel.2012.08.017","article-title":"A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo","volume":"23","author":"Davis","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1161\/CIRCRESAHA.110.235689","article-title":"Syndecan-4 prevents cardiac rupture and dysfunction after myocardial infarction","volume":"108","author":"Matsui","year":"2011","journal-title":"Circ. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1161\/HYPERTENSIONAHA.109.147256","article-title":"Syndecan-1: A critical mediator in cardiac fibrosis","volume":"55","author":"Frangogiannis","year":"2010","journal-title":"Hypertension"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1161\/CIRCULATIONAHA.106.644609","article-title":"Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction","volume":"115","author":"Vanhoutte","year":"2007","journal-title":"Circulation"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1161\/HYPERTENSIONAHA.109.137885","article-title":"Syndecan-1 amplifies angiotensin II-induced cardiac fibrosis","volume":"55","author":"Schellings","year":"2010","journal-title":"Hypertension"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.bbrc.2013.12.100","article-title":"The pdz-binding motif of yes-associated protein is required for its co-activation of tead-mediated CTGF transcription and oncogenic cell transforming activity","volume":"443","author":"Shimomura","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1161\/CIRCHEARTFAILURE.113.000846","article-title":"Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction","volume":"7","author":"Tromp","year":"2014","journal-title":"Circ. Heart Fail."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.1113\/jphysiol.2012.233593","article-title":"A distinct de novo expression of Nav1.5 sodium channels in human atrial fibroblasts differentiated into myofibroblasts","volume":"590","author":"Chatelier","year":"2012","journal-title":"J. Physiol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"H1231","DOI":"10.1152\/ajpheart.00878.2012","article-title":"Fibroblast katp currents modulate myocyte electrophysiology in infarcted hearts","volume":"304","author":"Benamer","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s00232-007-0027-8","article-title":"Contribution of BKCa-channel activity in human cardiac fibroblasts to electrical coupling of cardiomyocytes-fibroblasts","volume":"213","author":"Wang","year":"2006","journal-title":"J. Membr. Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1113\/jphysiol.2006.120832","article-title":"C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide c receptor-mediated signalling","volume":"580","author":"Rose","year":"2007","journal-title":"J. Physiol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.yjmcc.2012.10.016","article-title":"Trpv4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals","volume":"54","author":"Adapala","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_187","first-page":"9","article-title":"Molecular candidates for cardiac stretch-activated ion channels","volume":"2014","author":"Reed","year":"2014","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1748-1716.2010.02086.x","article-title":"Single mechano-gated channels activated by mechanical deformation of acutely isolated cardiac fibroblasts from rats","volume":"199","author":"Kamkin","year":"2010","journal-title":"Acta Physiol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.molmed.2015.12.006","article-title":"The living scar\u2014Cardiac fibroblasts and the injured heart","volume":"22","author":"Norris","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Numaga-Tomita, T., Kitajima, N., Kuroda, T., Nishimura, A., Miyano, K., Yasuda, S., Kuwahara, K., Sato, Y., Ide, T., and Birnbaumer, L. (2016). TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis. Sci. Rep., 6.","DOI":"10.1038\/srep39383"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"C562","DOI":"10.1152\/ajpcell.00187.2016","article-title":"TRPV4 ion channel is a novel regulator of dermal myofibroblast differentiation","volume":"312","author":"Sharma","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.1172\/JCI75331","article-title":"TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice","volume":"124","author":"Rahaman","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3324\/haematol.2013.086090","article-title":"Piezo1 plays a role in erythrocyte volume homeostasis","volume":"99","author":"Faucherre","year":"2014","journal-title":"Haematologica"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Ingber, D.E., Wang, N., and Stamenovic, D. (2014). Tensegrity, cellular biophysics, and the mechanics of living systems. Rep. Prog. Phys., 77.","DOI":"10.1088\/0034-4885\/77\/4\/046603"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/cm.20472","article-title":"Rho-kinase\/rock: A key regulator of the cytoskeleton and cell polarity","volume":"67","author":"Amano","year":"2010","journal-title":"Cytoskeleton"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1126\/science.285.5429.895","article-title":"Signaling from rho to the actin cytoskeleton through protein kinases rock and lim-kinase","volume":"285","author":"Maekawa","year":"1999","journal-title":"Science"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0092-8674(03)00278-2","article-title":"Actin dynamics control srf activity by regulation of its coactivator mal","volume":"113","author":"Miralles","year":"2003","journal-title":"Cell"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1128\/MCB.25.8.3173-3181.2005","article-title":"Muscle-specific signaling mechanism that links actin dynamics to serum response factor","volume":"25","author":"Kuwahara","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Mouilleron, S., Langer, C.A., Guettler, S., McDonald, N.Q., and Treisman, R. (2011). Structure of a pentavalent G-actin*MRTF-A complex reveals how G-actin controls nucleocytoplasmic shuttling of a transcriptional coactivator. Sci. Signal., 4.","DOI":"10.1126\/scisignal.2001750"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"H379","DOI":"10.1152\/ajpheart.01002.2013","article-title":"Nuclear Rhoa signaling regulates MRTF-dependent smc-specific transcription","volume":"307","author":"Staus","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1161\/CIRCRESAHA.110.223172","article-title":"Myocardin-related transcription factor-a controls myofibroblast activation and fibrosis in response to myocardial infarction","volume":"107","author":"Small","year":"2010","journal-title":"Circ. Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1172\/JCI66700","article-title":"Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis","volume":"123","author":"Zhou","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of yap\/taz in mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2013.07.042","article-title":"A mechanical checkpoint controls multicellular growth through YAP\/TAZ regulation by actin-processing factors","volume":"154","author":"Aragona","year":"2013","journal-title":"Cell"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1016\/j.cub.2014.07.034","article-title":"Regulation of yap by mechanical strain through JNK and hippo signaling","volume":"24","author":"Codelia","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cellsig.2016.10.002","article-title":"Synergistic induction of CTGF by cytochalasin D and TGF\u03b2-1 in primary human renal epithelial cells: Role of transcriptional regulators MK11, YAP\/TAZ and Smad2\/3","volume":"29","author":"Muehlich","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.cell.2007.07.019","article-title":"Elucidation of a universal size-control mechanism in drosophila and mammals","volume":"130","author":"Dong","year":"2007","journal-title":"Cell"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"34041","DOI":"10.1074\/jbc.M113.518019","article-title":"Phosphorylation of angiomotin by LATS1\/2 kinases inhibits f-actin binding, cell migration, and angiogenesis","volume":"288","author":"Dai","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1091\/mbc.e13-11-0701","article-title":"Angiomotins link f-actin architecture to hippo pathway signaling","volume":"25","author":"Paramasivam","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"L344","DOI":"10.1152\/ajplung.00300.2014","article-title":"Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis","volume":"308","author":"Liu","year":"2015","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.jhep.2015.04.011","article-title":"The hippo pathway effector YAP controls mouse hepatic stellate cell activation","volume":"63","author":"Mannaerts","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1016\/j.ajpath.2015.08.011","article-title":"YAP1 is a driver of myofibroblast differentiation in normal and diseased fibroblasts","volume":"185","author":"Piersma","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1164\/rccm.200812-1827OC","article-title":"Transcriptional coactivator with PDZ-binding motif is essential for normal alveolarization in mice","volume":"180","author":"Mitani","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"251","DOI":"10.7555\/JBR.28.20140020","article-title":"An emerging role for Hippo-YAP signaling in cardiovascular development","volume":"28","author":"Zhou","year":"2014","journal-title":"J. Biomed. Res."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/jid.2013.339","article-title":"Yap and taz regulate skin wound healing","volume":"134","author":"Lee","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Szeto, S.G., Narimatsu, M., Lu, M., He, X., Sidiqi, A.M., Tolosa, M.F., Chan, L., De Freitas, K., Bialik, J.F., and Majumder, S. (2016). YAP\/TAZ are mechanoregulators of TGF-\u03b2-smad signaling and renal fibrogenesis. J. Am. Soc. Nephrol.","DOI":"10.1681\/ASN.2015050499"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1101\/gad.1664408","article-title":"Tead mediates YAP-dependent gene induction and growth control","volume":"22","author":"Zhao","year":"2008","journal-title":"Genes Dev."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1016\/j.jmb.2015.04.015","article-title":"Crosstalk between hippo and TGFB: Subcellular localization of YAP\/TAZ\/SMAD complexes","volume":"427","author":"Grannas","year":"2015","journal-title":"J. Mol. Biol."},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Speight, P., Kofler, M., Szaszi, K., and Kapus, A. (2016). Context-dependent switch in chemo\/mechanotransduction via multilevel crosstalk among cytoskeleton-regulated MRTF and TAZ and TGF\u03b2-regulated SMAD3. Nat. Commun., 7.","DOI":"10.1038\/ncomms11642"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S0091-679X(10)98008-4","article-title":"Mechanical induction of gene expression in connective tissue cells","volume":"98","author":"Chan","year":"2010","journal-title":"Methods Cell Biol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nrm2594","article-title":"Mechanotransduction at a distance: Mechanically coupling the extracellular matrix with the nucleus","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1083\/jcb.200509124","article-title":"Coupling of the nucleus and cytoplasm: Role of the linc complex","volume":"172","author":"Crisp","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.pbiomolbio.2014.06.009","article-title":"Cellular mechanosensing: Getting to the nucleus of it all","volume":"115","author":"Fedorchak","year":"2014","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1242\/jcs.114.24.4485","article-title":"Nesprins: A novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues","volume":"114","author":"Zhang","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1002\/bies.20312","article-title":"Kash \u2019n karry: The KASH domain family of cargo-specific cytoskeletal adaptor proteins","volume":"27","author":"Starr","year":"2005","journal-title":"Bioessays"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1083\/jcb.200506083","article-title":"Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin","volume":"171","author":"Wilhelmsen","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"25805","DOI":"10.1074\/jbc.M313157200","article-title":"SUN2 is a novel mammalian inner nuclear membrane protein","volume":"279","author":"Hodzic","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"R708","DOI":"10.1016\/S0960-9822(99)80446-1","article-title":"The missing (L) UNC?","volume":"9","author":"Raff","year":"1999","journal-title":"Curr. Biol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1128\/MCB.26.10.3738-3751.2006","article-title":"SUN1 interacts with nuclear lamin a and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton","volume":"26","author":"Haque","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1080\/19491034.2016.1260802","article-title":"SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration","volume":"7","author":"Nishioka","year":"2016","journal-title":"Nucleus"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"18208","DOI":"10.1074\/jbc.M601980200","article-title":"The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain","volume":"281","author":"Caputo","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1083\/jcb.201409047","article-title":"Accessorizing and anchoring the linc complex for multifunctionality","volume":"208","author":"Chang","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1016\/j.biocel.2010.07.001","article-title":"Interfering with the connection between the nucleus and the cytoskeleton affects nuclear rotation, mechanotransduction and myogenesis","volume":"42","author":"Brosig","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1093\/hmg\/ddn386","article-title":"Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice","volume":"18","author":"Puckelwartz","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/19491034.2016.1183848","article-title":"The nuclear lamina in health and disease","volume":"7","author":"Dobrzynska","year":"2016","journal-title":"Nucleus"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1172\/JCI200419448","article-title":"Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A\/C-deficient mice","volume":"113","author":"Nikolova","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature12105","article-title":"Lamin A\/C and emerin regulate MKL1-SRF activity by modulating actin dynamics","volume":"497","author":"Ho","year":"2013","journal-title":"Nature"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bpj.2015.11.014","article-title":"Nesprin-2G, a component of the nuclear LINC complex, is subject to myosin-dependent tension","volume":"110","author":"Arsenovic","year":"2016","journal-title":"Biophys. J."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4161\/nucl.19090","article-title":"The nuclear envelope protein nesprin-2 has roles in cell proliferation and differentiation during wound healing","volume":"3","author":"Rashmi","year":"2012","journal-title":"Nucleus"},{"key":"ref_241","first-page":"9874","article-title":"Inner nuclear envelope protein sun1 plays a prominent role in mammalian mRNA export","volume":"43","author":"Li","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Alsarraj, J., Faraji, F., Geiger, T.R., Mattaini, K.R., Williams, M., Wu, J., Ha, N.H., Merlino, T., Walker, R.C., and Bosley, A.D. (2013). BRD4 short isoform interacts with RRP1B, SIPA1 and components of the linc complex at the inner face of the nuclear membrane. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080746"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1124\/mol.112.081661","article-title":"BET bromodomain proteins mediate downstream signaling events following growth factor stimulation in human lung fibroblasts and are involved in bleomycin-induced pulmonary fibrosis","volume":"83","author":"Tang","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"15713","DOI":"10.1073\/pnas.1522163112","article-title":"Brd4 is a novel therapeutic target for liver fibrosis","volume":"112","author":"Ding","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.3892\/etm.2015.2789","article-title":"Bet protein inhibition mitigates acute myocardial infarction damage in rats via the tlr4\/traf6\/nf-kappab pathway","volume":"10","author":"Sun","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.devcel.2007.03.018","article-title":"SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice","volume":"12","author":"Ding","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1016\/j.yexcr.2008.02.022","article-title":"Structural requirements for the assembly of linc complexes and their function in cellular mechanical stiffness","volume":"314","author":"Hale","year":"2008","journal-title":"Exp. Cell Res."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1161\/CIRCRESAHA.108.173989","article-title":"Nuclear shape, mechanics, and mechanotransduction","volume":"102","author":"Dahl","year":"2008","journal-title":"Circ. Res."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0021-9290(01)00201-9","article-title":"Contribution of the nucleus to the mechanical properties of endothelial cells","volume":"35","author":"Caille","year":"2002","journal-title":"J. Biomech."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1006\/bbrc.2000.2360","article-title":"Viscoelastic properties of the cell nucleus","volume":"269","author":"Guilak","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1073\/pnas.032668799","article-title":"Engineering gene expression and protein synthesis by modulation of nuclear shape","volume":"99","author":"Thomas","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s12195-013-0270-2","article-title":"Modulation of nuclear shape by substrate rigidity","volume":"6","author":"Lovett","year":"2013","journal-title":"Cell. Mol. Bioeng."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.gde.2012.11.006","article-title":"Chromatin organization and transcriptional regulation","volume":"23","author":"Hubner","year":"2013","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/nmat4729","article-title":"Transcription upregulation via force-induced direct stretching of chromatin","volume":"15","author":"Tajik","year":"2016","journal-title":"Nat. Mater."},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Furusawa, T., Rochman, M., Taher, L., Dimitriadis, E.K., Nagashima, K., Anderson, S., and Bustin, M. (2015). Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness. Nat. Commun., 6.","DOI":"10.1038\/ncomms7138"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.molcel.2009.07.002","article-title":"The interaction of NSBP1\/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription","volume":"35","author":"Rochman","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_257","doi-asserted-by":"crossref","unstructured":"Fang, L., Murphy, A.J., and Dart, A.M. (2017). A clinical perspective of anti-fibrotic therapies for cardiovascular disease. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00186"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(12)61855-8","article-title":"Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (relax-AHF): A randomised, placebo-controlled trial","volume":"381","author":"Teerlink","year":"2013","journal-title":"Lancet"},{"key":"ref_259","doi-asserted-by":"crossref","unstructured":"Friedman, S.L., Sheppard, D., Duffield, J.S., and Violette, S. (2013). Therapy for fibrotic diseases: Nearing the starting line. Sci. Transl. Med., 5.","DOI":"10.1126\/scitranslmed.3004700"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1083\/jcb.200201049","article-title":"The NH2-terminal peptide of \u03b1-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo","volume":"157","author":"Hinz","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_261","doi-asserted-by":"crossref","unstructured":"Yu-Wai-Man, C., Spencer-Dene, B., Lee, R.M., Hutchings, K., Lisabeth, E.M., Treisman, R., Bailly, M., Larsen, S.D., Neubig, R.R., and Khaw, P.T. (2017). Local delivery of novel MRTF\/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-00212-w"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.ajpath.2014.12.005","article-title":"Inhibition of myocardin-related transcription factor\/serum response factor signaling decreases lung fibrosis and promotes mesenchymal cell apoptosis","volume":"185","author":"Sisson","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1101\/gad.192856.112","article-title":"Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP","volume":"26","author":"Huang","year":"2012","journal-title":"Genes Dev."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1161\/CIRCRESAHA.115.306624","article-title":"Mir-206 mediates yap-induced cardiac hypertrophy and survival","volume":"117","author":"Yang","year":"2015","journal-title":"Circ. Res."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1128\/MCB.00154-10","article-title":"Myocardin-related transcription factor a is a common mediator of mechanical stress- and neurohumoral stimulation-induced cardiac hypertrophic signaling leading to activation of brain natriuretic peptide gene expression","volume":"30","author":"Kuwahara","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_266","first-page":"335","article-title":"Extracellular matrix elasticity directs stem cell differentiation","volume":"7","author":"Engler","year":"2007","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/cvr\/cvt338","article-title":"Reversible and irreversible differentiation of cardiac fibroblasts","volume":"101","author":"Driesen","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"9448","DOI":"10.1073\/pnas.1201840109","article-title":"Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis","volume":"109","author":"Kisseleva","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejphar.2014.04.007","article-title":"Reversal of myofibroblast differentiation: A review","volume":"734","author":"Yang","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nmat4780","article-title":"MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells","volume":"16","author":"Li","year":"2017","journal-title":"Nat. Mater."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1083\/jcb.201506055","article-title":"Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis","volume":"212","author":"Enemchukwu","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.jacc.2015.12.035","article-title":"Evidence for mechanisms underlying the functional benefits of a myocardial matrix hydrogel for post-mi treatment","volume":"67","author":"Wassenaar","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_273","doi-asserted-by":"crossref","unstructured":"Rodell, C.B., Lee, M.E., Wang, H., Takebayashi, S., Takayama, T., Kawamura, T., Arkles, J.S., Dusaj, N.N., Dorsey, S.M., and Witschey, W.R. (2016). Injectable shear-thinning hydrogels for minimally invasive delivery to infarcted myocardium to limit left ventricular remodeling. Circ. Cardiovasc. Interv., 9.","DOI":"10.1161\/CIRCINTERVENTIONS.116.004058"},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Perea-Gil, I., Prat-Vidal, C., and Bayes-Genis, A. (2015). In vivo experience with natural scaffolds for myocardial infarction: The times they are a-changin\u2019. Stem Cell Res. Ther., 6.","DOI":"10.1186\/s13287-015-0237-4"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.addr.2015.06.002","article-title":"Decellularized myocardial matrix hydrogels: In basic research and preclinical studies","volume":"96","author":"Wang","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.biomaterials.2015.12.002","article-title":"Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction","volume":"83","author":"Yoshizumi","year":"2016","journal-title":"Biomaterials"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.biomaterials.2014.12.021","article-title":"Delivery of an engineered hgf fragment in an extracellular matrix-derived hydrogel prevents negative lv remodeling post-myocardial infarction","volume":"45","author":"Sonnenberg","year":"2015","journal-title":"Biomaterials"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/6\/5\/53\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:36:19Z","timestamp":1760207779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/6\/5\/53"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,19]]},"references-count":277,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5]]}},"alternative-id":["jcm6050053"],"URL":"https:\/\/doi.org\/10.3390\/jcm6050053","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,19]]}}}