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CCN2 is a matricellular protein that appears to be important in scar formation.CCN2 mediates the pro-fibrotic effects in hypertrophic scars (HTSs) through an unknown mechanism; however, many activities of CCN2 protein are known to be mediated through direct binding to integrin receptors.In this study, we investigated the role of integrin α v β 3 in differentiation of hypertrophic scar fibroblasts (HTSF) induced by CCN2.First,we compared the levels of integrin α v β 3 between normal skin and hypertrophic scar (HTS)tissues, and found that integrin α v β3 was up-regulated in HTS.Second, we showed that CCN2 induces HTSF differentiation and collagen synthesis at the mRNAand protein levels.Based on these results, the expression of integrin α v β3 is up-regulated by CCN2stimulation during HTSF differentiation.Blockade of integrin α v β 3 prevented both CCN2-induced HTSF differentiation and collagen synthesis.Furthermore, the CCN2-induced increase in contractility of the HTSF in collagen lattices was inhibited by integrin α v β3 blocking antibodies.In conclusion, our study shows that integrin α v β3 contribute to pro-fibrotic CCN2 signaling.Blocking this pathway may be beneficial for the treatment of HTS.