{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:18:56Z","timestamp":1787242736756,"version":"build-2736575974"},"reference-count":107,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006438","name":"Office of the Assistant Secretary for Health","doi-asserted-by":"publisher","award":["W81XWH-18-1-0382"],"award-info":[{"award-number":["W81XWH-18-1-0382"]}],"id":[{"id":"10.13039\/100006438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006438","name":"Office of the Assistant Secretary for Health","doi-asserted-by":"publisher","award":["W81XWH-16-1-0679"],"award-info":[{"award-number":["W81XWH-16-1-0679"]}],"id":[{"id":"10.13039\/100006438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA244522"],"award-info":[{"award-number":["R01 CA244522"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["5T32AR052273"],"award-info":[{"award-number":["5T32AR052273"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a devastating skin blistering disease caused by mutations in the gene encoding type VII collagen (C7), leading to epidermal fragility, trauma-induced blistering, and long term, hard-to-heal wounds. Fibrosis develops rapidly in RDEB skin and contributes to both chronic wounds, which emerge after cycles of repetitive wound and scar formation, and squamous cell carcinoma\u2014the single biggest cause of death in this patient group. The molecular pathways disrupted in a broad spectrum of fibrotic disease are also disrupted in RDEB, and squamous cell carcinomas arising in RDEB are thus far molecularly indistinct from other sub-types of aggressive squamous cell carcinoma (SCC). Collectively these data demonstrate RDEB is a model for understanding the molecular basis of both fibrosis and rapidly developing aggressive cancer. A number of studies have shown that RDEB pathogenesis is driven by a radical change in extracellular matrix (ECM) composition and increased transforming growth factor-beta (TGF\u03b2) signaling that is a direct result of C7 loss-of-function in dermal fibroblasts. However, the exact mechanism of how C7 loss results in extensive fibrosis is unclear, particularly how TGF\u03b2 signaling is activated and then sustained through complex networks of cell-cell interaction not limited to the traditional fibrotic protagonist, the dermal fibroblast. Continued study of this rare disease will likely yield paradigms relevant to more common pathologies.<\/jats:p>","DOI":"10.3390\/ijms22105104","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:59:12Z","timestamp":1620817152000},"page":"5104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1403-7010","authenticated-orcid":false,"given":"Grace","family":"Tartaglia","sequence":"first","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, 233 S. 10th Street, BLSB 406, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6067-8209","authenticated-orcid":false,"given":"Qingqing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, 233 S. 10th Street, BLSB 406, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary M.","family":"Padron","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, 233 S. 10th Street, BLSB 406, Philadelphia, PA 19107, USA"},{"name":"The Joan and Joel Rosenbloom Research Center for Fibrotic Diseases, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"South","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, 233 S. 10th Street, BLSB 406, Philadelphia, PA 19107, USA"},{"name":"The Joan and Joel Rosenbloom Research Center for Fibrotic Diseases, Thomas Jefferson University, Philadelphia, PA 19107, USA"},{"name":"Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: Therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. 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