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FAK and Src are two important non-receptor tyrosine kinases that have been indicated in HS pathogenesis. Here we found both FAK and Src were activated in HS <jats:italic>vs.<\/jats:italic> normal skin (NS), NS fibroblasts treated with TGF-\u03b21 also exhibited FAK\/Src activation. Co-immunoprecipitation and dual-labelled immunofluorescence revealed an enhanced FAK-Src association and co-localization in HS <jats:italic>vs.<\/jats:italic> NS. To examine effects of FAK\/Src activation and their interplay on HS pathogenesis, site-directed mutagenesis followed by gene overexpression was conducted. Results showed only simultaneous overexpression of non-phosphorylatable mutant FAK Y407F and phosphomimetic mutant Src Y529E remarkably down-regulated the expression of Col I, Col III and \u03b1-SMA in cultured HS fibroblasts, alleviated extracellular matrix deposition and made collagen fibers more orderly in HS tissue <jats:italic>vs.<\/jats:italic> the effect from single transfection with wild-type or mutational FAK\/Src. Glabridin, a chemical found to block FAK-Src complex formation in cancers, exhibited therapeutic effects on HS pathology probably through co-deactivation of FAK\/Src which further resulted in FAK-Src de-association. This study suggests FAK-Src complex could serve as a potential molecular target and FAK\/Src double deactivation might be a novel strategy for HS therapy.<\/jats:p>","DOI":"10.1038\/srep26023","type":"journal-article","created":{"date-parts":[[2016,5,16]],"date-time":"2016-05-16T09:14:18Z","timestamp":1463390058000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Simultaneous deactivation of FAK and Src improves the pathology of hypertrophic scar"],"prefix":"10.1038","volume":"6","author":[{"given":"Linlin","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,16]]},"reference":[{"key":"BFsrep26023_CR1","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1111\/j.1524-475X.2007.00219.x","volume":"15","author":"A Armour","year":"2007","unstructured":"Armour, A., Scott, P. 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