{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:10:12Z","timestamp":1779088212065,"version":"3.51.4"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2021,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited blistering skin disease, resulting from biallelic mutations in\n                    <jats:italic>COL7A1,<\/jats:italic>\n                    the gene encoding type VII collagen (C7). At mucocutaneous barriers, tissue integrity relies upon linked extracellular matrix (ECM) proteins forming a physiologic suture, connecting basal epidermal keratinocytes to the underlying dermis. C7 secreted from epidermal keratinocytes and dermal fibroblasts homotrimerizes in the upper dermis to form anchoring fibrils, a critical component of this suture. Clinical manifestations of RDEB are apparent at birth and include exquisite skin fragility, pain and itch, high metabolic demand, and complications downstream of systemic inflammation. Dermal fibrosis is a critical complication of RDEB. Repeated cycles of mechanical injury and healing trigger characteristic fibrotic changes. In addition to functional limitations from joint strictures and pseudosyndactyly formation, dermal fibrosis in RDEB is a nidus for and potential driver of aggressive squamous cell carcinoma (SCC), the leading cause of death in RDEB. A greater understanding of fibrosis in RDEB promises to inform impactful, life\u2010prolonging clinical trials in this patient population with no proven systemic therapy or cure.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202114864","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T07:31:47Z","timestamp":1631518307000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deconstructing progressive inflammatory fibrosis in recessive dystrophic epidermolysis bullosa"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2430-911X","authenticated-orcid":false,"given":"Christen L","family":"Ebens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"BFEMMM202114864_CR1","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1016\/j.jid.2017.07.002","volume":"137","author":"V Alexeev","year":"2017","unstructured":"Alexeev V, Salas\u2010Alanis JC, Palisson F, Mukhtarzada L, Fortuna G, Uitto J, South A, Igoucheva O (2017) Pro\u2010inflammatory chemokines and cytokines dominate the blister fluid molecular signature in patients with epidermolysis bullosa and affect leukocyte and stem cell migration. J Invest Dermatol 137: 2298\u20132308","journal-title":"J Invest Dermatol"},{"key":"BFEMMM202114864_CR2","doi-asserted-by":"crossref","first-page":"e14392","DOI":"10.15252\/emmm.202114392","volume":"13","author":"R Bernasconi","year":"2021","unstructured":"Bernasconi R, Thriene K, Romero\u2010Fern\u00e1ndez E, Gretzmeier C, K\u00fchl T, Maler M, Nauroy P, Kleiser S, R\u00fchl\u2010Muth A\u2010C, Stumpe M et\u00a0al (2021) Pro\u2010inflammatory immunity supports fibrosis advancement in epidermolysis bullosa: intervention with Ang\u2010(1\u20137). EMBO Mol Med 13: e14392","journal-title":"EMBO Mol Med"},{"key":"BFEMMM202114864_CR3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.18632\/aging.100755","volume":"7","author":"JS Breitenbach","year":"2015","unstructured":"Breitenbach JS, Rinnerthaler M, Trost A, Weber M, Klausegger A, Gruber C, Bruckner D, Reitsamer HA, Bauer JW, Breitenbach M (2015) Transcriptome and ultrastructural changes in dystrophic Epidermolysis bullosa resemble skin aging. Aging 7: 389\u2013411","journal-title":"Aging"},{"key":"BFEMMM202114864_CR4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.matbio.2018.12.001","volume":"81","author":"F Cianfarani","year":"2019","unstructured":"Cianfarani F, De Domenico E, Nystr\u00f6m A, Mastroeni S, Abeni D, Baldini E, Ulisse S, Uva P, Bruckner\u2010Tuderman L, Zambruno G et\u00a0al (2019) Decorin counteracts disease progression in mice with recessive dystrophic epidermolysis bullosa. Matrix Biol 81: 3\u201316","journal-title":"Matrix Biol"},{"key":"BFEMMM202114864_CR5","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1111\/bjd.17858","volume":"181","author":"CL Ebens","year":"2019","unstructured":"Ebens CL, McGrath JA, Tamai K, Hovnanian A, Wagner JE, Riddle MJ, Keene DR, DeFor TE, Tryon R, Chen M et\u00a0al (2019) Bone marrow transplant with post\u2010transplant cyclophosphamide for recessive dystrophic epidermolysis bullosa expands the related donor pool and permits tolerance of non\u2010hematopoietic cellular grafts. Br J Dermatol 181: 1238\u20131246","journal-title":"Br J Dermatol"},{"key":"BFEMMM202114864_CR6","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, B\u00f6sl 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":"BFEMMM202114864_CR7","doi-asserted-by":"crossref","first-page":"15064","DOI":"10.1038\/s41598-020-71794-1","volume":"10","author":"I Fuentes","year":"2020","unstructured":"Fuentes I, Guttmann\u2010Gruber C, Tockner B, Diem A, Klausegger A, Cofr\u00e9\u2010Araneda G, Figuera O, Hidalgo Y, Morand\u00e9 P, Palisson F et\u00a0al (2020) Cells from discarded dressings differentiate chronic from acute wounds in patients with Epidermolysis Bullosa. Sci Rep 10: 15064","journal-title":"Sci Rep"},{"key":"BFEMMM202114864_CR8","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/biof.1587","volume":"46","author":"CR Harrell","year":"2020","unstructured":"Harrell CR, Markovic BS, Fellabaum C, Arsenijevic N, Djonov V, Volarevic V (2020) The role of Interleukin 1 receptor antagonist in mesenchymal stem cell\u2010based tissue repair and regeneration. BioFactors 46: 263\u2013275","journal-title":"BioFactors"},{"key":"BFEMMM202114864_CR9","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.15252\/emmm.201505061","volume":"7","author":"A Nystrom","year":"2015","unstructured":"Nystrom A, Thriene K, Mittapalli V, Kern JS, Kiritsi D, Dengjel J, Bruckner\u2010Tuderman L (2015) Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med 7: 1211\u20131228","journal-title":"EMBO Mol Med"},{"key":"BFEMMM202114864_CR10","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/stem.647","volume":"29","author":"J Tolar","year":"2011","unstructured":"Tolar J, Blazar BR, Wagner JE (2011) Concise review: Transplantation of human hematopoietic cells for extracellular matrix protein deficiency in epidermolysis bullosa. Stem Cells 29: 900\u2013906","journal-title":"Stem Cells"},{"key":"BFEMMM202114864_CR11","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/stem.3022","volume":"37","author":"S Vander Beken","year":"2019","unstructured":"Vander Beken S, de Vries JC, Meier\u2010Schiesser B, Meyer P, Jiang D, Sindrilaru A, Ferreira FF, Hainzl A, Schatz S, Muschhammer J et\u00a0al (2019) Newly defined ATP\u2010binding cassette subfamily B member 5 positive dermal mesenchymal stem cells promote healing of chronic iron\u2010overload wounds via secretion of interleukin\u20101 receptor antagonist. Stem Cells 37: 1057\u20131074","journal-title":"Stem Cells"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202114864.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.202114864","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.202114864\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.202114864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202114864.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:42:14Z","timestamp":1779086534000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.202114864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,13]]},"references-count":11,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10,7]]}},"alternative-id":["BFEMMM202114864"],"URL":"https:\/\/doi.org\/10.15252\/emmm.202114864","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,13]]},"assertion":[{"value":"10 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"EMMM202114864"}}