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Here, longitudinal analyses of the tissue proteome through the course of naturally developing disease in RDEB mice revealed that increased pro\u2010inflammatory immunity associates with fibrosis evolution. Mechanistically, this fibrosis is a consequence of altered extracellular matrix organization rather than that of increased abundance of major structural proteins. In a humanized system of disease progression, we targeted inflammatory cell fibroblast communication with Ang\u2010(1\u20107)\u2014an anti\u2010inflammatory heptapeptide of the renin\u2010angiotensin system, which reduced the fibrosis\u2010evoking aptitude of RDEB cells.\n                    <jats:italic>In vivo,<\/jats:italic>\n                    systemic administration of Ang\u2010(1\u20107) efficiently attenuated progression of multi\u2010organ fibrosis and increased survival of RDEB mice. Collectively, our study shows that selective down\u2010modulation of pro\u2010inflammatory immunity may mitigate injury\u2010induced fibrosis. Furthermore, together with published data, our data highlight molecular diversity among fibrotic conditions. Both findings have direct implications for the design of therapies addressing skin fragility and fibrosis.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202114392","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T03:50:45Z","timestamp":1630295445000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Pro\u2010inflammatory immunity supports fibrosis advancement in epidermolysis bullosa: intervention with Ang\u2010(1\u20107)"],"prefix":"10.1038","volume":"13","author":[{"given":"Rocco","family":"Bernasconi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7642-5078","authenticated-orcid":false,"given":"Kerstin","family":"Thriene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-0488","authenticated-orcid":false,"given":"Elena","family":"Romero\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gretzmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"K\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Maler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2092-2339","authenticated-orcid":false,"given":"Pauline","family":"Nauroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-1710","authenticated-orcid":false,"given":"Svenja","family":"Kleiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-1510","authenticated-orcid":false,"given":"Anne\u2010Catherine","family":"R\u00fchl\u2010Muth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stumpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-8981","authenticated-orcid":false,"given":"Dimitra","family":"Kiritsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan F","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-393X","authenticated-orcid":false,"given":"Boris","family":"Hinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-9093","authenticated-orcid":false,"given":"Leena","family":"Bruckner\u2010Tuderman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9453-4614","authenticated-orcid":false,"given":"J\u00f6rn","family":"Dengjel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-2240","authenticated-orcid":false,"given":"Alexander","family":"Nystr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"BFEMMM202114392_CR1","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1093\/hmg\/ddt514","volume":"23","author":"MJ Acu\u00f1a","year":"2014","unstructured":"Acu\u00f1a MJ, Pessina P, Olguin H, Cabrera D, Vio CP, Bader M, Mu\u00f1oz\u2010Canoves P, Santos RA, Cabello\u2010Verrugio C, Brandan E (2014) Restoration of muscle strength in dystrophic muscle by angiotensin\u20101\u20107 through inhibition of TGF\u2010\u03b2 signalling. 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