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So far, there are hardly any standardized and effective treatment options. Pathogenic mechanisms underlying fibrosis comprise excessive and uncontrolled myofibroblast differentiation, increased extracellular matrix protein (ECM) synthesis and an intensification of the forces exerted by the cytoskeleton. A deeper understanding of fibroblast transformation could help to prevent or reverse fibrosis by specifically interfering with abnormally regulated signaling pathways. The transcription factor NF-\u03baB has been implicated in the progression of fibrotic processes. However, the cellular processes regulated by NF-\u03baB in fibrosis as well as the NF-\u03baB isoforms preferentially involved are still completely unknown. In an in vitro model of fibrosis, we consistently observed the induction of the c-Rel subunit of NF-\u03baB. Functional abrogation of c-Rel by siRNA resulted in diminished cell contractility of dermal fibroblasts in relaxed, but not in stressed 3D collagen matrices. Furthermore, directed migration was reduced after c-Rel silencing and total N-cadherin expression level was diminished, possibly mediating the observed cellular defects. Therefore, NF-\u043aB c-Rel impacts central cellular adhesion markers and processes which negatively regulate fibrotic progression in SSc pathophysiology.<\/jats:p>","DOI":"10.1007\/s00403-021-02310-2","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T18:02:40Z","timestamp":1639072960000},"page":"943-951","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["NF-\u043aB c-Rel modulates pre-fibrotic changes in human fibroblasts"],"prefix":"10.1007","volume":"314","author":[{"given":"Lara Carolina","family":"Micus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska Susanne","family":"Trautschold-Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lena","family":"Jelit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Peter","family":"Sch\u00f6n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8867-8195","authenticated-orcid":false,"given":"Verena Natalie","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"issue":"7","key":"2310_CR1","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1038\/nm.2807","volume":"18","author":"TA Wynn","year":"2012","unstructured":"Wynn TA, Ramalingam TA (2012) Mechanisms of fibrosis: therapeutic translation for fibrotic disease. 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