The Role Of Secreted Protein,Acidic And Rich In Cysteine In The Fibrosis Of Cultured Human Tenon’s Fibroblasts Induced By Vascular Endothelial Growth Factor

Objective : Failure of glaucoma filtration surgery(GFS)is commonly attributed to scarring at the surgical site.The human Tenon’s fibroblast(HTF)is considered to be the major cell type contributing to the fibrotic response.Vascular endothelial growth factor(VEGF)and secreted protein,acidic and rich in cysteine(SPARC)are thought to be involved in angiogenesis and fibrosis.But its mechanism in GSF still remains to be further clarified.The purpose of this study was to examine the induction of SPARC by VEGF in cultured HTFs and examined whether specific inhibition of SPARC could influence the expression of pro-fibrotic factors such as collagen-I and matrix metalloproteinase-9(MMP-9)as well as the activity ERK pathway of HTFs stimulated by VEGF.Methods : Fibroblasts were obtained from the human tenon’s capsule tissues during strabismus surgery.In cultured HTF cells,when incubating with VEGF,the expression of SPARC and pro-fibrotic factors such as collagen-I,MMP-9 and the phosphorylation of ERK pathway were observed by western blot and RT-PCR analyses in normal or SPARC-silenced HTFs respectively.Results:In cultured HTFs,treated with VEGF,the expression of SPARC was slightly increased.The expression of pro-fibrotic factors including collagen-I,MMP-9,as well as the phosphorylation of ERK were also increased meanwhile.But this phenomenon was weaken in the SPARC-silenced HTFs compared with normal HTFs.Conclusions : Our data provided the evidence that SPARC contributes to wound healing and scar formation induced by VEGF in HTFs,may thus represent a novel target for anti-fibrotic strategies after filtration surgery.