{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:25:34Z","timestamp":1782800734325,"version":"3.54.5"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T00:00:00Z","timestamp":1600214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["CTQ2015-64402-C2-2-R"],"award-info":[{"award-number":["CTQ2015-64402-C2-2-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disease caused by mutation of the COL7A1 gene. RDEB is associated with high levels of TGF-\u03b21, which is likely to be involved in the fibrosis that develops in this disease. Endoglin (CD105) is a type III coreceptor for TGF-\u03b21 and its overexpression in fibroblasts deregulates physiological Smad\/Alk1\/Alk5 signalling, repressing the synthesis of TGF-\u03b21 and extracellular matrix (ECM) proteins. Raloxifene is a specific estrogen receptor modulator designated as an orphan drug for hereditary hemorrhagic telangiectasia, a rare vascular disease. Raloxifene stimulates endoglin synthesis, which could attenuate fibrosis. By contrast, the antioxidant N-acetylcysteine may have therapeutic value to rectify inflammation, fibrosis and endothelial dysfunction. Thus, we present here a repurposing strategy based on the molecular and functional screening of fibroblasts from RDEB patients with these drugs, leading us to propose the repositioning of these two well-known drugs currently in clinical use, raloxifene and N-acetylcysteine, to counteract fibrosis and inflammation in RDEB. Both compounds modulate the profibrotic events that may ultimately be responsible for the clinical manifestations in RDEB, suggesting that these findings may also be relevant for other diseases in which fibrosis is an important pathophysiological event.<\/jats:p>","DOI":"10.3390\/cells9092108","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T10:30:12Z","timestamp":1600252212000},"page":"2108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Raloxifene and n-Acetylcysteine Ameliorate TGF-Signalling in Fibroblasts from Patients with Recessive Dominant Epidermolysis Bullosa"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4339-0443","authenticated-orcid":false,"given":"Tania","family":"Aguado","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedicine, Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas, U-707 CIBERER, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departament of Biomedical Engineering, Universidad Carlos III, 28911 Madrid, Spain"},{"name":"Spanish Network of Research Groups on Rare Diseases (CIBERER) U714, 28911 Madrid, Spain"},{"name":"Foundation of the Institute for Health Research, Jim\u00e9nez D\u00edaz Foundation, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departament of Biomedical Engineering, Universidad Carlos III, 28911 Madrid, Spain"},{"name":"Spanish Network of Research Groups on Rare Diseases (CIBERER) U714, 28911 Madrid, Spain"},{"name":"Foundation of the Institute for Health Research, Jim\u00e9nez D\u00edaz Foundation, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Ferrer-Mayorga","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-2364","authenticated-orcid":false,"given":"Luc\u00eda","family":"Mart\u00ednez-Santamar\u00eda","sequence":"additional","affiliation":[{"name":"Departament of Biomedical Engineering, Universidad Carlos III, 28911 Madrid, Spain"},{"name":"Spanish Network of Research Groups on Rare Diseases (CIBERER) U714, 28911 Madrid, Spain"},{"name":"Foundation of the Institute for Health Research, Jim\u00e9nez D\u00edaz Foundation, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"del R\u00edo","sequence":"additional","affiliation":[{"name":"Departament of Biomedical Engineering, Universidad Carlos III, 28911 Madrid, Spain"},{"name":"Spanish Network of Research Groups on Rare Diseases (CIBERER) U714, 28911 Madrid, Spain"},{"name":"Foundation of the Institute for Health Research, Jim\u00e9nez D\u00edaz Foundation, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6310-2245","authenticated-orcid":false,"given":"Luisa-Mar\u00eda","family":"Botella","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas, U-707 CIBERER, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Mar\u00eda","family":"S\u00e1nchez-Puelles","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas, U-707 CIBERER, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.jaad.2014.01.903","article-title":"Inherited epidermolysis bullosa: Updated recommendations on diagnosis and classification","volume":"70","author":"Fine","year":"2014","journal-title":"J. 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