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However, whether it is an effective drug target in hypertrophic scar treatment is still not known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>In the present study, we observed that SIRT1 localized to both the epidermis and the dermis of skin tissues by immunohistochemistry. After knock\u2010down of SIRT1 by shRNA or up\u2010regulating SIRT1 by resveratrol, the expression of \u03b1\u2010SMA, Col1 and Col3 in fibroblasts were detected by western blots. A mouse excision wound healing model was used to observe the changes in collagen fibre associated with the different expression levels of SIRT1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>SIRT1 expression was inhibited in hypertrophic scar tissue. The down\u2010regulation of SIRT1 resulted in an increased expression of \u03b1\u2010SMA, Col1 and Col3 in hypertrophic scar\u2010derived fibroblasts. In contrast, the up\u2010regulation of SIRT1 not only inhibited the expression of \u03b1\u2010SMA, Col1 and Col3 in hypertrophic scar\u2010derived fibroblasts but also blocked the activation of TGF\u03b21\u2010induced normal skin\u2010derived fibroblasts. In the mouse model of wound healing, the deletion of SIRT1 resulted in denser collagen fibres and a more disordered structure, whereas resveratrol treatment led to a more organized and thinner collagen fibre, which was similar to that observed during normal wound healing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The results revealed that SIRT1 negatively regulates TGF\u03b21\u2010induced fibroblast activation and inhibits excessive scar formation and is, therefore, a promising drug target for hypertrophic scar formation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13460","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T22:37:56Z","timestamp":1455835076000},"page":"1589-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Identification of sirtuin 1 as a promising therapeutic target for hypertrophic 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