Inhibition By Triptolide Of Transforming Growth Factor-?–induced Collagen Gel Contraction Mediated By Human Tenon Fibroblasts

Purpose: The successful outcome of glaucoma filtration surgery is dependent upon the wound-healing response at the surgical site.Scar formation due to excessive synthesis of new extracellular matrix(ECM)and contraction of subconjunctival tissue at the filtering bleb site is thought to be the principal cause of surgery failure.Transforming growth factor(TGF)-? plays an essential role in conjunctival scarring,specifically following glaucoma surgery.The effects of triptolide,the major constituent of extracts of the herb Tripterygium wilfordii hook f,on the contractility of human Tenon fibroblasts(HTFs)and extracellular matrix(ECM)synthesis by these cells cultured in a three-dimensional collagen gel were investigated.Methods: HTFs were cultured in three-dimensional gels of type I collagen and in the absence or presence of transforming growth factor(TGF)-? or triptolide.Collagen gel contraction was evaluated by measurement of gel diameter.The expression of intergrins and ?–smooth muscle actin(?-SMA)were examined by immunoblot analysis.Fibronectin were measured with immunoassays.Results: Triptolide inhibited TGF-?-induced collagen gel contraction mediated by HTF in a concentration-and time-dependent manner.TGF-?–induced phosphorylation of MLC was attenuated by triptolide.Furthermore,Triptolide suppressed the production of fibronectin induced by TGF-?.Exposure of the cells to various concentrations of triptolide for 3 days had no effect on the release of LDH,indicative of a lack of cytotoxicity.Conclusions: Triptolide inhibited TGF-?-induced contractility of HTFs and fibronectin synthesis by these cells.Triptolide might thus prove effective for inhibition of scar formation after glaucoma filtration surgery.