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Hypertrophic scar contracture is considered to be a pathologic and exaggerated wound healing response that is known to be triggered by repetitive mechanical forces. We now show that Transient Receptor Potential (TRP) C3 regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFkB pathway. TRPC3 is highly expressed in human hypertrophic scar tissue and mechanical stimuli are known to upregulate TRPC3 expression in human skin fibroblasts <jats:italic>in vitro<\/jats:italic>. TRPC3 overexpressing fibroblasts subjected to repetitive stretching forces showed robust expression levels of fibronectin. Furthermore, mechanical stretching of TRPC3 overexpressing fibroblasts induced the activation of nuclear factor-kappa B (NF\u03baB), a regulator fibronectin expression, which was able to be attenuated by pharmacologic blockade of either TRPC3 or NF\u03baB. Finally, transplantation of TRPC3 overexpressing fibroblasts into mice promoted wound contraction and increased fibronectin levels <jats:italic>in vivo<\/jats:italic>. These observations demonstrate that mechanical stretching drives fibronectin expression via the TRPC3-NFkB axis, leading to intractable wound contracture. This model explains how mechanical strain on cutaneous wounds might contribute to pathologic scarring.<\/jats:p>","DOI":"10.1038\/srep11620","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T09:53:13Z","timestamp":1435225993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFkB activation"],"prefix":"10.1038","volume":"5","author":[{"given":"Hisako","family":"Ishise","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrett","family":"Larson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soh","family":"Nishimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tateki","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyuki","family":"Kanazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Sotsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutoshi","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Kakibuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,25]]},"reference":[{"key":"BFsrep11620_CR1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.2741\/1184","volume":"9","author":"RF Diegelmann","year":"2004","unstructured":"Diegelmann, R. 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