SIRT1 is a NAD-dependent protein deacetylase that participate in cellular regulation. The increased migration of fibroblast is important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial whether SIRT1 act as an activator or suppressor for cell migration. We have therefore established the role of SIRT1 in human dermal fibroblast migration and explored target of SIRT1 for dermal fibroblast migration.Results
SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation of TGF-β further induced expression SIRT1 and Cyr61. Treatment of resveratol (RSV), SIRT1 agonist or overexpression of SIRT1 also promoted expression of SIRT1 and Cyr61 in human dermal fibroblasts, whereas inhibition of SIRT1 activity by nicotinamide or knock down of SIRT1 down-regulated Cyr61 basal level as well as TGF-β or RSV-induced Cyr61expression. Blocking of ERK signalling by PD98509 reduced TGF-β or RSV-induced Cyr61 expression. TGF-β, RSV or SIRT1 vector enhanced β-catenin as well as Cyr61 expression. This stimulation was reduced by Wnt inhibitor, XAV939. RSV increased migration and nicotinamide attenuated RSV-induced migration of human dermal fibroblasts. Furthermore, SIRT1 overexpression promoted cell migration whereas blocking Cyr61 attenuated SIRT1-stimulated migration of human dermal fibroblasts.Conclusion
SIRT1 increased cell migration by stimulated Cyr61 expression for their target through the ERK and Wnt/β-catenin signalling. SIRT1-induced Cyr61 production is very important for human dermal fibroblasts migration.