{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:56:59Z","timestamp":1790621819776,"version":"4.1.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T00:00:00Z","timestamp":1437350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T00:00:00Z","timestamp":1437350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 850\u2010B08"],"award-info":[{"award-number":["SFB 850\u2010B08"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["Nr. DE1757\/3\u20101"],"award-info":[{"award-number":["Nr. DE1757\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["BR1475\/12\u20101"],"award-info":[{"award-number":["BR1475\/12\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["1795\/1\u20101"],"award-info":[{"award-number":["1795\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011960","name":"DEBRA International","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011960","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Federal Ministry for Education and Research"},{"name":"E\u2010RARE\u20102"},{"name":"ERA\u2010Net for Research on Rare Diseases"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)\u2014a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence\u2010based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF\u2010\u03b2 activity is elevated in injured RDEB skin, we targeted TGF\u2010\u03b2 activity with losartan in a preclinical setting. Long\u2010term treatment of RDEB mice efficiently reduced TGF\u2010\u03b2 signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan\u2010 vs. vehicle\u2010treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF\u2010\u03b1 and IL\u20106 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF\u2010\u03b2\u2010mediated inflammation, and matrix remodeling. Inhibition of TGF\u2010\u03b2 activity\u00a0limits these unwanted outcomes and thereby substantially ameliorates long\u2010term symptoms.<\/jats:p>","DOI":"10.15252\/emmm.201505061","type":"journal-article","created":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T21:15:19Z","timestamp":1437426919000},"page":"1211-1228","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms"],"prefix":"10.1038","volume":"7","author":[{"given":"Alexander","family":"Nystr\u00f6m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Thriene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venugopal","family":"Mittapalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes S","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Kiritsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"Dengjel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Bruckner\u2010Tuderman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,20]]},"reference":[{"key":"BFEMMM201505061_CR1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3810","volume":"11","author":"RJ Akhurst","year":"2012","unstructured":"Akhurst RJ, Hata A (2012) Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discovery 11: 790\u2013811","journal-title":"Nat Rev Drug Discovery"},{"key":"BFEMMM201505061_CR2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.det.2009.10.020","volume":"28","author":"L Bruckner\u2010Tuderman","year":"2010","unstructured":"Bruckner\u2010Tuderman L (2010) Dystrophic epidermolysis bullosa: pathogenesis and clinical features. Dermatol Clin 28: 107\u2013114","journal-title":"Dermatol Clin"},{"key":"BFEMMM201505061_CR3","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1046\/j.1523-1755.1999.00597.x","volume":"56","author":"JM Campistol","year":"1999","unstructured":"Campistol JM, Inigo P, Jimenez W, Lario S, Clesca PH, Oppenheimer F, Rivera F (1999) Losartan decreases plasma levels of TGF\u2010beta1 in transplant patients with chronic allograft nephropathy. Kidney Int 56: 714\u2013719","journal-title":"Kidney Int"},{"key":"BFEMMM201505061_CR4","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.det.2009.10.011","volume":"28","author":"HJ Chung","year":"2010","unstructured":"Chung HJ, Uitto J (2010) Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol Clin 28: 93\u2013105","journal-title":"Dermatol Clin"},{"key":"BFEMMM201505061_CR5","doi-asserted-by":"crossref","first-page":"G726","DOI":"10.1152\/ajpgi.00162.2009","volume":"297","author":"J Colmenero","year":"2009","unstructured":"Colmenero J, Bataller R, Sancho\u2010Bru P, Dominguez M, Moreno M, Forns X, Bruguera M, Arroyo V, Brenner DA, Gines P (2009) Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C. Am J Physiol Gastrointest Liver Physiol 297: G726\u2013G734","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"BFEMMM201505061_CR6","first-page":"1329","volume":"124","author":"JR Cook","year":"2014","unstructured":"Cook JR, Carta L, Benard L, Chemaly ER, Chiu E, Rao SK, Hampton TG, Yurchenco P, Gen TACRC, Costa KD et\u00a0al (2014) Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome. J Clin Invest 124: 1329\u20131339","journal-title":"J Clin Invest"},{"key":"BFEMMM201505061_CR500","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","volume":"26","author":"J Cox","year":"2008","unstructured":"Cox J, Mann M (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.\u2010range mass accuracies and proteome\u2010wide protein quantification. Nat Biotechnol 26: 1367\u20131372","journal-title":"Nat Biotechnol"},{"key":"BFEMMM201505061_CR501","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1021\/pr101065j","volume":"10","author":"J Cox","year":"2011","unstructured":"Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M (2011) Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res 10: 1794\u20131805","journal-title":"J Proteome Res"},{"key":"BFEMMM201505061_CR7","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.jaad.2014.05.038","volume":"71","author":"P Davila\u2010Seijo","year":"2014","unstructured":"Davila\u2010Seijo P, Hernandez\u2010Martin A, Morcillo\u2010Makow E, Rajan C, Garcia\u2010Doval I (2014) Current dystrophic epidermolysis bullosa research does not match research needs perceived by patients and clinicians. J Am Acad Dermatol 71: 1008\u20131011","journal-title":"J Am Acad Dermatol"},{"key":"BFEMMM201505061_CR8","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1172\/JCI42014","volume":"120","author":"HC Dietz","year":"2010","unstructured":"Dietz HC (2010) TGF\u2010beta in the pathogenesis and prevention of disease: a matter of aneurysmic proportions. J Clin Invest 120: 403\u2013407","journal-title":"J Clin Invest"},{"key":"BFEMMM201505061_CR9","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.jaad.2014.01.903","volume":"70","author":"JD Fine","year":"2014","unstructured":"Fine JD, Bruckner\u2010Tuderman L, Eady RA, Bauer EA, Bauer JW, Has C, Heagerty A, Hintner H, Hovnanian A, Jonkman MF et\u00a0al (2014) Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 70: 1103\u20131126","journal-title":"J Am Acad Dermatol"},{"key":"BFEMMM201505061_CR10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jaad.2008.09.035","volume":"60","author":"JD Fine","year":"2009","unstructured":"Fine JD, Johnson LB, Weiner M, Li KP, Suchindran C (2009) Epidermolysis bullosa and the risk of life\u2010threatening cancers: the National EB Registry experience, 1986\u20132006. J Am Acad Dermatol 60: 203\u2013211","journal-title":"J Am Acad Dermatol"},{"key":"BFEMMM201505061_CR11","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1172\/JCI34292","volume":"118","author":"A Fritsch","year":"2008","unstructured":"Fritsch A, Loeckermann S, Kern JS, Braun A, Bosl MR, Bley TA, Schumann H, von Elverfeldt D, Paul D, Erlacher M et\u00a0al (2008) A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy. J Clin Invest 118: 1669\u20131679","journal-title":"J Clin Invest"},{"key":"BFEMMM201505061_CR12","doi-asserted-by":"crossref","first-page":"e55427","DOI":"10.1371\/journal.pone.0055427","volume":"8","author":"G Gay\u2010Jordi","year":"2013","unstructured":"Gay\u2010Jordi G, Guash E, Benito B, Brugada J, Nattel S, Mont L, Serrano\u2010Mollar A (2013) Losartan prevents heart fibrosis induced by long\u2010term intensive exercise in an animal model. PLoS ONE 8: e55427","journal-title":"PLoS ONE"},{"key":"BFEMMM201505061_CR13","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nm.3544","volume":"20","author":"I Grafe","year":"2014","unstructured":"Grafe I, Yang T, Alexander S, Homan EP, Lietman C, Jiang MM, Bertin T, Munivez E, Chen Y, Dawson B et\u00a0al (2014) Excessive transforming growth factor\u2010beta signaling is a common mechanism in osteogenesis imperfecta. Nat Med 20: 670\u2013675","journal-title":"Nat Med"},{"issue":"Suppl 1","key":"BFEMMM201505061_CR14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2165\/1153427-S0-000000000-00000","volume":"11","author":"E Gubinelli","year":"2010","unstructured":"Gubinelli E, Angelo C, Pacifico V (2010) A case of dystrophic epidermolysis bullosa improved with etanercept for concomitant psoriatic arthritis. Am J Clin Dermatol 11(Suppl 1): 53\u201354","journal-title":"Am J Clin Dermatol"},{"key":"BFEMMM201505061_CR15","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1126\/science.1192152","volume":"332","author":"JP Habashi","year":"2011","unstructured":"Habashi JP, Doyle JJ, Holm TM, Aziz H, Schoenhoff F, Bedja D, Chen Y, Modiri AN, Judge DP, Dietz HC (2011) Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Science 332: 361\u2013365","journal-title":"Science"},{"key":"BFEMMM201505061_CR16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1126\/science.1124287","volume":"312","author":"JP Habashi","year":"2006","unstructured":"Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C et\u00a0al (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312: 117\u2013121","journal-title":"Science"},{"key":"BFEMMM201505061_CR17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1600-065X.2009.00794.x","volume":"230","author":"NC Henderson","year":"2009","unstructured":"Henderson NC, Sethi T (2009) The regulation of inflammation by galectin\u20103. Immunol Rev 230: 160\u2013171","journal-title":"Immunol Rev"},{"key":"BFEMMM201505061_CR18","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s11926-009-0017-1","volume":"11","author":"B Hinz","year":"2009","unstructured":"Hinz B (2009) Tissue stiffness, latent TGF\u2010beta1 activation, and mechanical signal transduction: implications for the pathogenesis and treatment of fibrosis. Curr Rheumatol Rep 11: 120\u2013126","journal-title":"Curr Rheumatol Rep"},{"key":"BFEMMM201505061_CR19","doi-asserted-by":"crossref","first-page":"5932","DOI":"10.1038\/ncomms6932","volume":"6","author":"E Hoste","year":"2015","unstructured":"Hoste E, Arwert EN, Lal R, South AP, Salas\u2010Alanis JC, Murrell DF, Donati G, Watt FM (2015) Innate sensing of microbial products promotes wound\u2010induced skin cancer. Nat Commun 6: 5932","journal-title":"Nat Commun"},{"key":"BFEMMM201505061_CR20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40257-013-0059-z","volume":"15","author":"CK Hsu","year":"2014","unstructured":"Hsu CK, Wang SP, Lee JY, McGrath JA (2014) Treatment of hereditary epidermolysis bullosa: updates and future prospects. Am J Clin Dermatol 15: 1\u20136","journal-title":"Am J Clin Dermatol"},{"key":"BFEMMM201505061_CR21","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/nm0496-418","volume":"2","author":"Y Isaka","year":"1996","unstructured":"Isaka Y, Brees DK, Ikegaya K, Kaneda Y, Imai E, Noble NA, Border WA (1996) Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney. Nat Med 2: 418\u2013423","journal-title":"Nat Med"},{"key":"BFEMMM201505061_CR22","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1067\/msy.2000.105858","volume":"127","author":"YC Jang","year":"2000","unstructured":"Jang YC, Tsou R, Gibran NS, Isik FF (2000) Vitronectin deficiency is associated with increased wound fibrinolysis and decreased microvascular angiogenesis in mice. Surgery 127: 696\u2013704","journal-title":"Surgery"},{"key":"BFEMMM201505061_CR23","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1111\/j.1538-7836.2007.02745.x","volume":"5","author":"Y Kanno","year":"2007","unstructured":"Kanno Y, Kuroki A, Okada K, Tomogane K, Ueshima S, Matsuo O, Matsuno H (2007) Alpha2\u2010antiplasmin is involved in the production of transforming growth factor beta1 and fibrosis. J Thromb Haemost 5: 2266\u20132273","journal-title":"J Thromb Haemost"},{"key":"BFEMMM201505061_CR24","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1182\/blood-2005-10-009191","volume":"108","author":"JS Kim","year":"2006","unstructured":"Kim JS, Kim JG, Moon MY, Jeon CY, Won HY, Kim HJ, Jeon YJ, Seo JY, Kim JI, Kim J et\u00a0al (2006) Transforming growth factor\u2010beta1 regulates macrophage migration via RhoA. Blood 108: 1821\u20131829","journal-title":"Blood"},{"key":"BFEMMM201505061_CR25","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/(SICI)1096-9896(199802)184:2<212::AID-PATH996>3.0.CO;2-Z","volume":"184","author":"T Kojima","year":"1998","unstructured":"Kojima T, Miyaishi O, Saga S, Ishiguro N, Tsutsui Y, Iwata H (1998) The retention of abnormal type I procollagen and correlated expression of HSP 47 in fibroblasts from a patient with lethal osteogenesis imperfecta. J Pathol 184: 212\u2013218","journal-title":"J Pathol"},{"key":"BFEMMM201505061_CR26","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1053\/hupa.2001.29675","volume":"32","author":"GK Koukoulis","year":"2001","unstructured":"Koukoulis GK, Shen J, Virtanen I, Gould VE (2001) Vitronectin in the cirrhotic liver: an immunomarker of mature fibrosis. Hum Pathol 32: 1356\u20131362","journal-title":"Hum Pathol"},{"key":"BFEMMM201505061_CR27","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/msb.2013.17","volume":"9","author":"V Kuttner","year":"2013","unstructured":"Kuttner V, Mack C, Rigbolt KT, Kern JS, Schilling O, Busch H, Bruckner\u2010Tuderman L, Dengjel J (2013) Global remodelling of cellular microenvironment due to loss of collagen VII. Mol Syst Biol 9: 657","journal-title":"Mol Syst Biol"},{"key":"BFEMMM201505061_CR28","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1056\/NEJMoa1404731","volume":"371","author":"RV Lacro","year":"2014","unstructured":"Lacro RV, Dietz HC, Sleeper LA, Yetman AT, Bradley TJ, Colan SD, Pearson GD, Selamet Tierney ES, Levine JC, Atz AM et\u00a0al (2014) Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med 371: 2061\u20132071","journal-title":"N Engl J Med"},{"key":"BFEMMM201505061_CR29","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1096\/fj.03-1273rev","volume":"18","author":"A Leask","year":"2004","unstructured":"Leask A, Abraham DJ (2004) TGF\u2010beta signaling and the fibrotic response. FASEB J 18: 816\u2013827","journal-title":"FASEB J"},{"key":"BFEMMM201505061_CR30","doi-asserted-by":"crossref","first-page":"19059","DOI":"10.1074\/jbc.272.30.19059","volume":"272","author":"S Lee","year":"1997","unstructured":"Lee S, Solow\u2010Cordero DE, Kessler E, Takahara K, Greenspan DS (1997) Transforming growth factor\u2010beta regulation of bone morphogenetic protein\u20101\/procollagen C\u2010proteinase and related proteins in fibrogenic cells and keratinocytes. J Biol Chem 272: 19059\u201319066","journal-title":"J Biol Chem"},{"key":"BFEMMM201505061_CR31","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1161\/01.CIR.103.6.789","volume":"103","author":"DS Lim","year":"2001","unstructured":"Lim DS, Lutucuta S, Bachireddy P, Youker K, Evans A, Entman M, Roberts R, Marian AJ (2001) Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation 103: 789\u2013791","journal-title":"Circulation"},{"key":"BFEMMM201505061_CR32","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1371\/journal.pgen.0040007","volume":"4","author":"TS Lisse","year":"2008","unstructured":"Lisse TS, Thiele F, Fuchs H, Hans W, Przemeck GK, Abe K, Rathkolb B, Quintanilla\u2010Martinez L, Hoelzlwimmer G, Helfrich M et\u00a0al (2008) ER stress\u2010mediated apoptosis in a new mouse model of osteogenesis imperfecta. PLoS Genet 4: e7","journal-title":"PLoS Genet"},{"key":"BFEMMM201505061_CR33","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.drudis.2014.09.022","volume":"20","author":"BL Loeys","year":"2015","unstructured":"Loeys BL (2015) Angiotensin receptor blockers: a panacea for Marfan syndrome and related disorders? Drug Discov Today 20: 262\u2013266","journal-title":"Drug Discov Today"},{"key":"BFEMMM201505061_CR34","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/pmic.201300422","volume":"14","author":"C Montaldo","year":"2014","unstructured":"Montaldo C, Mattei S, Baiocchini A, Rotiroti N, Del Nonno F, Pucillo LP, Cozzolino AM, Battistelli C, Amicone L, Ippolito G et\u00a0al (2014) Spike\u2010in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload. Proteomics 14: 1107\u20131115","journal-title":"Proteomics"},{"key":"BFEMMM201505061_CR35","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S1359-6101(99)00029-5","volume":"11","author":"JE Murphy\u2010Ullrich","year":"2000","unstructured":"Murphy\u2010Ullrich JE, Poczatek M (2000) Activation of latent TGF\u2010beta by thrombospondin\u20101: mechanisms and physiology. Cytokine Growth Factor Rev 11: 59\u201369","journal-title":"Cytokine Growth Factor Rev"},{"key":"BFEMMM201505061_CR36","doi-asserted-by":"crossref","first-page":"F278","DOI":"10.1152\/ajprenal.00139.2003","volume":"286","author":"T Naito","year":"2004","unstructured":"Naito T, Masaki T, Nikolic\u2010Paterson DJ, Tanji C, Yorioka N, Kohno N (2004) Angiotensin II induces thrombospondin\u20101 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF\u2010beta1. Am J Physiol Renal Physiol 286: F278\u2013F287","journal-title":"Am J Physiol Renal Physiol"},{"key":"BFEMMM201505061_CR37","first-page":"3522","volume":"72","author":"YZ Ng","year":"2012","unstructured":"Ng YZ, Pourreyron C, Salas\u2010Alanis JC, Dayal JH, Cepeda\u2010Valdes R, Yan W, Wright S, Chen M, Fine JD, Hogg FJ et\u00a0al (2012) Fibroblast\u2010derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa. Cancer Res 72: 3522\u20133534","journal-title":"Cancer Res"},{"key":"BFEMMM201505061_CR38","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1172\/JCI68127","volume":"123","author":"A Nystrom","year":"2013","unstructured":"Nystrom A, Velati D, Mittapalli VR, Fritsch A, Kern JS, Bruckner\u2010Tuderman L (2013) Collagen VII plays a dual role in wound healing. J Clin Invest 123: 3498\u20133509","journal-title":"J Clin Invest"},{"key":"BFEMMM201505061_CR39","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1093\/hmg\/ddu102","volume":"23","author":"T Odorisio","year":"2014","unstructured":"Odorisio T, Di Salvio M, Orecchia A, Di Zenzo G, Piccinni E, Cianfarani F, Travaglione A, Uva P, Bellei B, Conti A et\u00a0al (2014) Monozygotic twins discordant for recessive dystrophic epidermolysis bullosa phenotype highlight the role of TGF\u2010beta signalling in modifying disease severity. Hum Mol Genet 23: 3907\u20133922","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201505061_CR40","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/j.amjcard.2013.06.019","volume":"112","author":"C Pees","year":"2013","unstructured":"Pees C, Laccone F, Hagl M, Debrauwer V, Moser E, Michel\u2010Behnke I (2013) Usefulness of losartan on the size of the ascending aorta in an unselected cohort of children, adolescents, and young adults with Marfan syndrome. Am J Cardiol 112: 1477\u20131483","journal-title":"Am J Cardiol"},{"key":"BFEMMM201505061_CR41","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1111\/bjd.12599","volume":"169","author":"G Petrof","year":"2013","unstructured":"Petrof G, Martinez\u2010Queipo M, Mellerio JE, Kemp P, McGrath JA (2013) Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle\u2010controlled trial. Br J Dermatol 169: 1025\u20131033","journal-title":"Br J Dermatol"},{"key":"BFEMMM201505061_CR42","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s12026-012-8286-6","volume":"52","author":"G Radosavljevic","year":"2012","unstructured":"Radosavljevic G, Volarevic V, Jovanovic I, Milovanovic M, Pejnovic N, Arsenijevic N, Hsu DK, Lukic ML (2012) The roles of Galectin\u20103 in autoimmunity and tumor progression. Immunol Res 52: 100\u2013110","journal-title":"Immunol Res"},{"key":"BFEMMM201505061_CR43","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.coph.2012.02.007","volume":"12","author":"F Ramirez","year":"2012","unstructured":"Ramirez F, Rifkin DB (2012) Is losartan the drug for all seasons? Curr Opin Pharmacol 12: 223\u2013224","journal-title":"Curr Opin Pharmacol"},{"key":"BFEMMM201505061_CR44","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1038\/nprot.2007.261","volume":"2","author":"J Rappsilber","year":"2007","unstructured":"Rappsilber J, Mann M, Ishihama Y (2007) Protocol for micro\u2010purification, enrichment, pre\u2010fractionation and storage of peptides for proteomics using StageTips. Nat Protoc 2: 1896\u20131906","journal-title":"Nat Protoc"},{"key":"BFEMMM201505061_CR45","first-page":"787","volume":"12","author":"D Seiffert","year":"1997","unstructured":"Seiffert D (1997) Constitutive and regulated expression of vitronectin. Histol Histopathol 12: 787\u2013797","journal-title":"Histol Histopathol"},{"key":"BFEMMM201505061_CR46","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1074\/jbc.271.10.5474","volume":"271","author":"D Seiffert","year":"1996","unstructured":"Seiffert D, Curriden SA, Jenne D, Binder BR, Loskutoff DJ (1996) Differential regulation of vitronectin in mice and humans in\u00a0vitro. J Biol Chem 271: 5474\u20135480","journal-title":"J Biol Chem"},{"key":"BFEMMM201505061_CR47","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1038\/nprot.2006.468","volume":"1","author":"A Shevchenko","year":"2006","unstructured":"Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M (2006) In\u2010gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc 1: 2856\u20132860","journal-title":"Nat Protoc"},{"key":"BFEMMM201505061_CR48","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-62703-227-8_10","volume":"961","author":"A Sprenger","year":"2013","unstructured":"Sprenger A, Kuttner V, Bruckner\u2010Tuderman L, Dengjel J (2013) Global proteome analyses of SILAC\u2010labeled skin cells. Methods Mol Biol 961: 179\u2013191","journal-title":"Methods Mol Biol"},{"key":"BFEMMM201505061_CR49","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0304-3835(95)90160-4","volume":"89","author":"D Sun","year":"1995","unstructured":"Sun D, Kar S, Carr BI (1995) Differentially expressed genes in TGF\u2010beta 1\u00a0sensitive and resistant human hepatoma cells. Cancer Lett 89: 73\u201379","journal-title":"Cancer Lett"},{"key":"BFEMMM201505061_CR50","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","volume":"43","author":"D Szklarczyk","year":"2015","unstructured":"Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta\u2010Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP et\u00a0al (2015) STRING v10: protein\u2010protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43: D447\u2013D452","journal-title":"Nucleic Acids Res"},{"key":"BFEMMM201505061_CR51","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1053\/jhep.2002.32679","volume":"36","author":"Y Terui","year":"2002","unstructured":"Terui Y, Saito T, Watanabe H, Togashi H, Kawata S, Kamada Y, Sakuta S (2002) Effect of angiotensin receptor antagonist on liver fibrosis in early stages of chronic hepatitis C. Hepatology 36: 1022","journal-title":"Hepatology"},{"key":"BFEMMM201505061_CR52","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.4049\/jimmunol.179.10.7079","volume":"179","author":"Y Tsuruta","year":"2007","unstructured":"Tsuruta Y, Park YJ, Siegal GP, Liu G, Abraham E (2007) Involvement of vitronectin in lipopolysaccaride\u2010induced acute lung injury. J Immunol 179: 7079\u20137086","journal-title":"J Immunol"},{"key":"BFEMMM201505061_CR53","doi-asserted-by":"crossref","first-page":"22537","DOI":"10.1074\/jbc.M102352200","volume":"276","author":"MI Uzel","year":"2001","unstructured":"Uzel MI, Scott IC, Babakhanlou\u2010Chase H, Palamakumbura AH, Pappano WN, Hong HH, Greenspan DS, Trackman PC (2001) Multiple bone morphogenetic protein 1\u2010related mammalian metalloproteinases process pro\u2010lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures. J Biol Chem 276: 22537\u201322543","journal-title":"J Biol Chem"},{"key":"BFEMMM201505061_CR54","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1136\/jmg.2006.045302","volume":"44","author":"R Varki","year":"2007","unstructured":"Varki R, Sadowski S, Uitto J, Pfendner E (2007) Epidermolysis bullosa. II. Type VII collagen mutations and phenotype\u2010genotype correlations in the dystrophic subtypes. J Med Genet 44: 181\u2013192","journal-title":"J Med Genet"},{"issue":"898\u2013908","key":"BFEMMM201505061_CR55","first-page":"e897","volume":"69","author":"SS Venugopal","year":"2013","unstructured":"Venugopal SS, Yan W, Frew JW, Cohn HI, Rhodes LM, Tran K, Melbourne W, Nelson JA, Sturm M, Fogarty J et\u00a0al (2013) A phase II randomized vehicle\u2010controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol 69(898\u2013908): e897","journal-title":"J Am Acad Dermatol"},{"key":"BFEMMM201505061_CR56","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1056\/NEJMoa0910501","volume":"363","author":"JE Wagner","year":"2010","unstructured":"Wagner JE, Ishida\u2010Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, Chen M, Riddle MJ, Osborn MJ, Lund T et\u00a0al (2010) Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med 363: 629\u2013639","journal-title":"N Engl J Med"},{"key":"BFEMMM201505061_CR57","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature12345","volume":"499","author":"X Wang","year":"2013","unstructured":"Wang X, Abraham S, McKenzie JA, Jeffs N, Swire M, Tripathi VB, Luhmann UF, Lange CA, Zhai Z, Arthur HM et\u00a0al (2013a) LRG1 promotes angiogenesis by modulating endothelial TGF\u2010beta signalling. Nature 499: 306\u2013311","journal-title":"Nature"},{"key":"BFEMMM201505061_CR58","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1038\/mt.2013.87","volume":"21","author":"X Wang","year":"2013","unstructured":"Wang X, Ghasri P, Amir M, Hwang B, Hou Y, Khalili M, Lin A, Keene D, Uitto J, Woodley DT et\u00a0al (2013b) Topical application of recombinant type VII collagen incorporates into the dermal\u2010epidermal junction and promotes wound closure. Mol Ther 21: 1335\u20131344","journal-title":"Mol Ther"},{"key":"BFEMMM201505061_CR59","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/0161-5890(93)90111-N","volume":"30","author":"MG Wing","year":"1993","unstructured":"Wing MG, Seilly DJ, Bridgman DJ, Harrison RA (1993) Rapid isolation and biochemical characterization of rat C1 and C1q. Mol Immunol 30: 433\u2013440","journal-title":"Mol Immunol"},{"key":"BFEMMM201505061_CR60","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1007\/s001099900028","volume":"77","author":"G Wolf","year":"1999","unstructured":"Wolf G, Ziyadeh FN, Stahl RA (1999) Angiotensin II stimulates expression of transforming growth factor beta receptor type II in cultured mouse proximal tubular cells. J Mol Med (Berl) 77: 556\u2013564","journal-title":"J Mol Med (Berl)"},{"key":"BFEMMM201505061_CR503","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.1021\/pr4007969","volume":"12","author":"M Zarei","year":"2013","unstructured":"Zarei M, Sprenger A, Gretzmeier C, Dengjel J (2013) Rapid combinatorial ERLIC\u2010SCX solid\u2010phase extraction for in\u2010depth phosphoproteome analysis. J Proteome Res 12: 5989\u20135995","journal-title":"J Proteome Res"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201505061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.201505061","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.201505061\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.201505061","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201505061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:16:09Z","timestamp":1779084969000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.201505061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,20]]},"references-count":63,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9,1]]}},"alternative-id":["BFEMMM201505061"],"URL":"https:\/\/doi.org\/10.15252\/emmm.201505061","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,20]]},"assertion":[{"value":"23 January 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}