Role of Integrin alphavbeta3 in differentiation of human hypertrophic scar fibroblasts induced by co

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  Connective tissue growth factor (CTGF) is a matricellular protein that appears to play an important role in scar formation.CTGF is a mediator of the pro-fibrotic effects of TGF-β in cultured cells,but the specific function of CTGF in the fibrotic process has not been elucidated.Many activities of CTGF protein are mediated through its direct binding to integrin receptors.In this study we investigated the role of integrin alphavbeta3 in differentiation of hypertrophic scar fibroblasts (HTSF) induced by CTGF.First,we compared the levels of alphav、beta3 integrins between atrophic scar(AS) and hypertrophic scar(HTS).we found that alphav、beta3 integrins were up-regulated in HTS.Second,we show that CTGF induces HTSF differentiation and collagen synthesis in mRNA and protein level.Based on the results,we demonstrated the expression of alphav、beta3 integrins mRNA was up-regulated by CTGF stimulation during the HTSF differentiation.Then,blockade of the alphavbeta3 integrins prevents the CTGF induced HTSF differentiation and collagen synthesis.Furthermore,the increased contractility of the HTSF in the collagen lattices induced by CTGF was inhibited by the Integrin alphavbeta3 blocking antibodies.In conclusion,our study defines the alphavbeta3 integrin that contributes to the pro-fibrotic CTGF signaling and suggests that blockade of this pathway may be beneficial for the treatment of HTS.
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