Hepatocyte growth factor suppresses the overproduction of α-SMA induced by TGF-β1 in rat medial collateral ligament fibroblasts

Objective:To examine the effectiveness of HGF in blocking TGF-β1-inducedα-SMA production in rat medial collateral ligament(MCL)fibroblasts.Method:Fibroblasts were obtained from rat MCL.Cell culture was supplemented with 5ng/ml of TGF-β1 along with increasing doses of HGF(10-40 ng/ml).After 72 hours incubation,the productions ofα-SMA and Smad3 mRNA were assayed by RT-PCR.Expression ofα-SMA protein was assessed by immunostaining.Result:Treatment with TGF-β1 significantly stimulatedα-SMA and Smad3 mRNA production in MCL fibroblasts(P0.01).Remarkably,the addition of HGF reduced productions of all components induced by TGF-β1 in a dose-dependent manner(P0.05).Conclusion:HGF antagonizes TGF-β1 inducedα-SMA production in MCL fibroblasts by down regulating Smad3.The findings provide a cellular and molecular basis for HGF′s acting as a therapeutic agent for MCL scar and fibrosis formation.