{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:41:02Z","timestamp":1790804462759,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marche Biobank Project","award":["POR FESR 2014 - 2020"],"award-info":[{"award-number":["POR FESR 2014 - 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic sclerosis (SSc) is a clinically heterogeneous disorder of the connective tissue characterized by vascular alterations, immune\/inflammatory manifestations, and organ fibrosis. SSc pathogenesis is complex and still poorly understood. Therefore, effective therapies are lacking and remain nonspecific and limited to disease symptoms. In the last few years, many molecular and cellular mediators of SSc fibrosis have been described, providing new potential options for targeted therapies. In this review: (i) we focused on the PDGF\/PDGFR pathway as key signaling molecules in the development of tissue fibrosis; (ii) we highlighted the possible role of stimulatory anti-PDGFR\u03b1 autoantibodies in the pathogenesis of SSc; (iii) we reported the most promising PDGF\/PDGFR targeting therapies.<\/jats:p>","DOI":"10.3390\/ijms23073904","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:34:29Z","timestamp":1648762469000},"page":"3904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["PDGF\/PDGFR: A Possible Molecular Target in Scleroderma Fibrosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-7408","authenticated-orcid":false,"given":"Chiara","family":"Paolini","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-6325","authenticated-orcid":false,"given":"Silvia","family":"Agarbati","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devis","family":"Benfaremo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"},{"name":"Department of Internal Medicine, Clinica Medica, Ospedali Riuniti \u201cUmberto I-G.M. Lancisi-G. Salesi\u201d, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9835-8446","authenticated-orcid":false,"given":"Matteo","family":"Mozzicafreddo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6863-2600","authenticated-orcid":false,"given":"Silvia","family":"Svegliati","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Moroncini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"},{"name":"Department of Internal Medicine, Clinica Medica, Ospedali Riuniti \u201cUmberto I-G.M. Lancisi-G. Salesi\u201d, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/BOR.0000000000000785","article-title":"Scleroderma epidemiology update","volume":"33","author":"Calderon","year":"2021","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5301\/jsrd.5000249","article-title":"Pathogenesis of systemic sclerosis: Recent insights of molecular and cellular mechanisms and therapeutic opportunities","volume":"2","author":"Varga","year":"2017","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1177\/2397198319894851","article-title":"Circulating biomarkers of systemic sclerosis\u2014Interstitial lung disease","volume":"5","author":"Fretheim","year":"2020","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/2397198320903867","article-title":"Pathogenesis of systemic sclerosis associated interstitial lung disease","volume":"5","author":"Nihtyanova","year":"2020","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.humimm.2016.10.017","article-title":"Genomic and genetic studies of systemic sclerosis: A systematic review","volume":"78","author":"Chairta","year":"2017","journal-title":"Hum. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"826839","DOI":"10.3389\/fphar.2022.826839","article-title":"Contributions of Immune Cells and Stromal Cells to the Pathogenesis of Systemic Sclerosis: Recent Insights","volume":"13","author":"Dai","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"822804","DOI":"10.3389\/fmed.2021.822804","article-title":"Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine","volume":"8","author":"Kuret","year":"2021","journal-title":"Front. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Szabo, I., Muntean, L., Crisan, T., Rednic, V., Sirbe, C., and Rednic, S. (2021). Novel Concepts in Systemic Sclerosis Pathogenesis: Role for miRNAs. Biomedicines, 9.","DOI":"10.3390\/biomedicines9101471"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10067-019-04564-8","article-title":"Use of vasoactive\/vasodilating drugs for systemic sclerosis (SSc)-related digital ulcers (DUs) in expert tertiary centres: Results from the analysis of the observational real-life DeSScipher study","volume":"39","author":"Blagojevic","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1136\/annrheumdis-2016-209909","article-title":"Update of EULAR recommendations for the treatment of systemic sclerosis","volume":"76","author":"Fransen","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","first-page":"1596","article-title":"Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. Reply","volume":"381","author":"Distler","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1101\/gad.1653708","article-title":"Role of platelet-derived growth factors in physiology and medicine","volume":"22","author":"Andrae","year":"2008","journal-title":"Genes. Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1152\/physrev.1999.79.4.1283","article-title":"Mechanism of action and in vivo role of platelet-derived growth factor","volume":"79","author":"Heldin","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1159\/000495594","article-title":"Different PDGF Receptor Dimers Drive Distinct Migration Modes of the Mouse Skin Fibroblast","volume":"51","author":"Yamada","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2017.03.003","article-title":"PDGFs and their receptors","volume":"614","author":"Kazlauskas","year":"2017","journal-title":"Gene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cytogfr.2004.03.003","article-title":"PDGF signaling in cells and mice","volume":"15","author":"Tallquist","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.mam.2017.11.008","article-title":"PDGF in organ fibrosis","volume":"62","author":"Klinkhammer","year":"2018","journal-title":"Mol. Aspects Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.21037\/atm-21-5638","article-title":"PDGF-BB promotes vascular smooth muscle cell migration by enhancing Pim-1 expression via inhibiting miR-214","volume":"9","author":"Zhou","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.4065\/81.9.1241","article-title":"Biology of platelet-derived growth factor and its involvement in disease","volume":"Volume 81","author":"Alvarez","year":"2006","journal-title":"Mayo Clinic Proceedings"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1042\/BST20200004","article-title":"The emerging complexity of PDGFRs: Activation, internalization and signal attenuation","volume":"48","author":"Rogers","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0092-8674(93)90232-F","article-title":"Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor\u2019s mitogenic signal","volume":"73","author":"Valius","year":"1993","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/35078555","article-title":"Regulation of c-myc expression by PDGF through Rho GTPases","volume":"3","author":"Chiariello","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1016\/j.bbapap.2012.10.015","article-title":"Platelet-derived growth factors and their receptors: Structural and functional perspectives","volume":"1834","author":"Chen","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.devcel.2008.12.003","article-title":"Increased PDGFRalpha activation disrupts connective tissue development and drives systemic fibrosis","volume":"16","author":"Olson","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.exer.2009.11.003","article-title":"Recent developments in our understanding of how platelet-derived growth factor (PDGF) and its receptors contribute to proliferative vitreoretinopathy","volume":"90","author":"Lei","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1007\/s00018-020-03753-y","article-title":"PDGF receptor mutations in human diseases","volume":"78","author":"Guerit","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/pin.12530","article-title":"Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor","volume":"67","author":"Ishii","year":"2017","journal-title":"Pathol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/164_2016_80","article-title":"Platelet-Derived Growth Factor in Heart Failure","volume":"243","author":"Medamana","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-7113-8_1","article-title":"Human Fibrotic Diseases: Current Challenges in Fibrosis Research","volume":"1627","author":"Rosenbloom","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41584-019-0322-7","article-title":"Shared and distinct mechanisms of fibrosis","volume":"15","author":"Distler","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. (2020). Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells, 9.","DOI":"10.3390\/cells9040875"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s12551-020-00734-0","article-title":"Growth factor therapy for cardiac repair: An overview of recent advances and future directions","volume":"12","author":"White","year":"2020","journal-title":"Biophys. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.yexcr.2016.10.022","article-title":"PDGF-A and PDGF-B induces cardiac fibrosis in transgenic mice","volume":"349","author":"Gallini","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nature20160","article-title":"Intronic polyadenylation of PDGFRalpha in resident stem cells attenuates muscle fibrosis","volume":"540","author":"Mueller","year":"2016","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"745308","DOI":"10.3389\/fimmu.2021.745308","article-title":"PDGF Promotes Dermal Fibroblast Activation via a Novel Mechanism Mediated by Signaling Through MCHR1","volume":"12","author":"Takamura","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13075-015-0575-8","article-title":"Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis","volume":"17","author":"Clark","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1084\/jem.175.5.1227","article-title":"Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts","volume":"175","author":"Yamakage","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_38","first-page":"1876","article-title":"Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma","volume":"22","author":"Ludwicka","year":"1995","journal-title":"J. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Liu, T., Zhang, J., Zhang, J., Mu, X., Su, H., Hu, X., Liu, W., Zhao, E., and Li, W. (2013). RNA interference against platelet-derived growth factor receptor alpha mRNA inhibits fibroblast transdifferentiation in skin lesions of patients with systemic sclerosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060414"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1093\/rheumatology\/ket254","article-title":"Alteration of circulating miRNAs in SSc: miR-30b regulates the expression of PDGF receptor beta","volume":"52","author":"Tanaka","year":"2013","journal-title":"Rheumatology"},{"key":"ref_41","first-page":"e58922","article-title":"Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin","volume":"30","author":"Orlando","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1056\/NEJMoa052955","article-title":"Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis","volume":"354","author":"Baroni","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.1346-8138.2009.00762.x","article-title":"Autoantibody profiles in systemic sclerosis: Predictive value for clinical evaluation and prognosis","volume":"37","author":"Hamaguchi","year":"2010","journal-title":"J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.coi.2007.11.004","article-title":"Pathogenic autoantibodies in systemic sclerosis","volume":"19","author":"Gabrielli","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"ref_45","first-page":"3","article-title":"Role of viral infections in the etiopathogenesis of systemic sclerosis","volume":"31","author":"Moroncini","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1002\/art.39125","article-title":"Epitope Specificity Determines Pathogenicity and Detectability of Anti-Platelet-Derived Growth Factor Receptor alpha Autoantibodies in Systemic Sclerosis","volume":"67","author":"Moroncini","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ab.2017.04.011","article-title":"Characterization of binding and quantification of human autoantibodies to PDGFRalpha using a biosensor-based approach","volume":"528","author":"Moroncini","year":"2017","journal-title":"Anal. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.imlet.2017.10.007","article-title":"Agonistic antibodies in systemic sclerosis","volume":"195","author":"Moroncini","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_49","first-page":"75","article-title":"Agonistic Anti-PDGF Receptor Autoantibodies from Patients with Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In Vitro","volume":"8","author":"Svegliati","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1002\/art.39728","article-title":"Induction of Scleroderma Fibrosis in Skin-Humanized Mice by Administration of Anti-Platelet-Derived Growth Factor Receptor Agonistic Autoantibodies","volume":"68","author":"Luchetti","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.cell.2021.01.036","article-title":"Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry","volume":"184","author":"Kschonsak","year":"2021","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11307","DOI":"10.1073\/pnas.1000806107","article-title":"Structures of a platelet-derived growth factor\/propeptide complex and a platelet-derived growth factor\/receptor complex","volume":"107","author":"Shim","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.cell.2007.05.055","article-title":"Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor","volume":"130","author":"Yuzawa","year":"2007","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.str.2016.12.012","article-title":"Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A","volume":"25","author":"Stuttfeld","year":"2017","journal-title":"Structure"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1002\/j.1460-2075.1992.tb05485.x","article-title":"Crystal structure of human platelet-derived growth factor BB","volume":"11","author":"Oefner","year":"1992","journal-title":"EMBO J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.bbrc.2016.06.117","article-title":"Structural and biochemical studies of the PDGFRA kinase domain","volume":"477","author":"Liang","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mam.2017.11.007","article-title":"The PDGF\/PDGFR pathway as a drug target","volume":"62","author":"Papadopoulos","year":"2018","journal-title":"Mol. Aspects Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1021\/bi5015425","article-title":"Characterization of binding mode of action of a blocking anti-platelet-derived growth factor (PDGF)-B monoclonal antibody, MOR8457, reveals conformational flexibility and avidity needed for PDGF-BB to bind PDGF receptor-beta","volume":"54","author":"Kuai","year":"2015","journal-title":"Biochemistry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.hrthm.2013.03.014","article-title":"Inhibition of platelet-derived growth factor-AB signaling prevents electromechanical remodeling of adult atrial myocytes that contact myofibroblasts","volume":"10","author":"Musa","year":"2013","journal-title":"Heart Rhythm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1755-1536-6-10","article-title":"Platelet-derived growth factor alpha and beta receptors have overlapping functional activities towards fibroblasts","volume":"6","author":"Donovan","year":"2013","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1158\/1535-7163.MCT-12-0431","article-title":"Stromal platelet-derived growth factor receptor alpha (PDGFRalpha) provides a therapeutic target independent of tumor cell PDGFRalpha expression in lung cancer xenografts","volume":"11","author":"Gerber","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"833","DOI":"10.2147\/OTT.S127609","article-title":"Developments in the management of advanced soft-tissue sarcoma\u2014Olaratumab in context","volume":"11","author":"Moroncini","year":"2018","journal-title":"Onco Targets Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/jama.2020.1707","article-title":"Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial","volume":"323","author":"Tap","year":"2020","journal-title":"JAMA"},{"key":"ref_64","first-page":"357027","article-title":"Imatinib: A breakthrough of targeted therapy in cancer","volume":"2014","author":"Iqbal","year":"2014","journal-title":"Chemother. Res. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.trsl.2021.01.001","article-title":"Tyrosine kinases in the pathogenesis of tissue fibrosis in systemic sclerosis and potential therapeutic role of their inhibition","volume":"231","author":"Mendoza","year":"2021","journal-title":"Transl. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1172\/JCI200419603","article-title":"Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis","volume":"114","author":"Daniels","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/art.22314","article-title":"Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis","volume":"56","author":"Distler","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.semarthrit.2012.06.001","article-title":"Therapeutic inhibition of tyrosine kinases in systemic sclerosis: A review of published experience on the first 108 patients treated with imatinib","volume":"Volume 42","author":"Bournia","year":"2013","journal-title":"Seminars in Arthritis and Rheumatism"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"R144","DOI":"10.1186\/ar4606","article-title":"Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: A phase II pilot study","volume":"16","author":"Fraticelli","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.jid.2018.08.021","article-title":"Notch Signaling Activity Determines Uptake and Biological Effect of Imatinib in Systemic Sclerosis Dermal Fibroblasts","volume":"139","author":"Harrach","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.jid.2017.03.032","article-title":"Blockade of PDGF Receptors by Crenolanib Has Therapeutic Effect in Patient Fibroblasts and in Preclinical Models of Systemic Sclerosis","volume":"137","author":"Makino","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102444","DOI":"10.1016\/j.jaut.2020.102444","article-title":"CXCL4 triggers monocytes and macrophages to produce PDGF-BB, culminating in fibroblast activation: Implications for systemic sclerosis","volume":"111","author":"Carvalheiro","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Martyanov, V., Kim, G.J., Hayes, W., Du, S., Ganguly, B.J., Sy, O., Lee, S.K., Bogatkevich, G.S., Schieven, G.L., and Schiopu, E. (2017). Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187580"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13075-015-0721-3","article-title":"Nilotinib (Tasigna) in the treatment of early diffuse systemic sclerosis: An open-label, pilot clinical trial","volume":"17","author":"Gordon","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4774","DOI":"10.1158\/0008-5472.CAN-07-6307","article-title":"BIBF 1120: Triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy","volume":"68","author":"Hilberg","year":"2008","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","article-title":"Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis","volume":"370","author":"Richeldi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1136\/annrheumdis-2014-207109","article-title":"Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis","volume":"75","author":"Huang","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Benfaremo, D., Svegliati, S., Paolini, C., Agarbati, S., and Moroncini, G. (2022). Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010163"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1056\/NEJMoa1908681","article-title":"Nintedanib in Progressive Fibrosing Interstitial Lung Diseases","volume":"381","author":"Flaherty","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S2213-2600(20)30036-9","article-title":"Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: A randomised, double-blind, placebo-controlled, parallel-group trial","volume":"8","author":"Wells","year":"2020","journal-title":"Lancet Respir. 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