title: Identification of sirtuin 1 as a promising therapeutic target for hypertrophic scars.
abstract: Sirtuin1 (SIRT1), the founding member of mammalian class III histone deacetylases, is reported to be a drug target involved in fibrotic diseases. However, whether it is an effective drug target in hypertrophic scar treatment is still not known.
  
  
  
  In the present study, we observed that SIRT1 localized to both the epidermis and the dermis of skin tissues by immunohistochemistry. After knock-down of SIRT1 by shRNA or up-regulating SIRT1 by resveratrol, the expression of α-SMA, 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.
  
  
  
  SIRT1 expression was inhibited in hypertrophic scar tissue. The down-regulation of SIRT1 resulted in an increased expression of α-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts. In contrast, the up-regulation of SIRT1 not only inhibited the expression of α-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts but also blocked the activation of TGFβ1-induced normal skin-derived 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.
  
  
  
  The results revealed that SIRT1 negatively regulates TGFβ1-induced fibroblast activation and inhibits excessive scar formation and is, therefore, a promising drug target for hypertrophic scar formation.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiao-Zhi
authors.initials: XZ
authors.lastname: Bai
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Long-Long
authors.initials: LL
authors.lastname: Yang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Su
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shi
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Chao-Wu
authors.initials: CW
authors.lastname: Tang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000235:genetics; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D034741:RNA, Small Interfering; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol