Effect Of Hepatocyte Growth Factor On Proliferation And Apoptosis Of Rat Hepatic Stellate Cell In Vitro And The Study Of Its Anti-fibrotic Mechanism

Objective: 1.To investigate the effect of hepatocyte growth factor(HGF) on proliferation and apoptosis of rat hepatic stellate cell line-99(rHSC-99) in vitro;2. To study the effect of HGF on the content of collagen type I and the gene expression of matrix metalloproteinase 13(MMP-13)and tissue inhibitor of metalloproteinase 1 (TIMP-1) in rHSC-99.Methods: A rat hepatic stellate cell line, rHSC-99, was treated with hepatocyte growth factor. The content of collagen type I was examined by ELISA;cell proliferation was assessed by MTT colorimetric assay;the apoptosis was detected by Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL );RT-PCR and immuocytochemistry were used to detect mRNA and protein of MMP-13 and TIMP-1 of rHSC-99.Results: 1.Administration rhHGF could significantly reduced the content of collagen type I in rHSC-99 in dose-dependent manner(P <0.01). 2. HGF could suppress HSC proliferation induced by platelet-derived growth factor(PDGF)(P <0.01)and induce HSC apoptosis(P <0.05). 3. Treatment of rHSC-99 cells with HGF resulted in a dose dependent increase in MMP-13 mRNA and protein expression,it was at peak for administration of 100 ng/ml HGF (P <0.01),although TIMP-1 mRNA and protein were not affected (P >0.05).Conclusions:HGF could significantly reduced the content of collagen type I in rHSC-99;HGF could suppress HSC proliferation induced by PDGF and induce HSC apoptosis; HGF could increase expression of MMP-13 mRNA and protein.All of these biological effects of HGF on HSC were associated with recovery from liver fibrosis in rats.