The mechanism by which bone marrow mesenchymal stem cells participate in apoptosis of hepatic stellate cells / 中国组织工程研究

ABSTRACT

BACKGROUND:Control of hepatic stelate cel activation and proliferation is the focus of developing strategies against liver fibrosis. Human or murine bone marrow mesenchymal stem cels can induce apoptosis of hepatic stelate cels through paracrine of hepatocyte growth factors. OBJECTIVE:To explore the mechanism by which bone marrow mesenchymal stem cels participate in apoptosis of rat hepatic stelate cels. METHODS:Hepatic stelate cels and bone marrow mesenchymal stem cels were seeded and co-cultured in the upper and lower chambers in a co-culture system, serving as a co-culture group. In the blank control group, only hepatic stelate cels were involved. In the c-Met inhibitor group, hepatic stelate cels and bone marrow mesenchymal stem cels were treated with 3 mg/L C-Met inhibitor. In the RhoA inhibitor group, both kinds of cels were treated with 3 mg/L RhoA inhibitor. RESULTS AND CONCLUSION:The concentration of c-Met inhibitor was 3.0 mg/L. RhoA inhibitor at 30μmol/L exhibited a greater inhibitory effect than at other concentrations. RhoA mRNA and protein expression in the co-culture, c-Met inhibitor and in particular RhoA inhibitor groups was obviously greater than in the blank control group. Hepatocyte growth factor concentration in each group was gradualy decreased with time, hepatocyte growth factor activator concentration in each group was gradualy increased with time, and the changes were most obvious in the c-Met inhibitor group. Apoptosis rate of hepatic stelate cels in each group was gradualy increased with time, and highest apoptosis rate appeared in the RhoA inhibitor group, and lowest apoptosis rate in the c-Met inhibitor group. These findings suggest that bone marrow mesenchymal stem cels participate in and promote the apoptosis of hepatic stelate cels by activating hepatocyte growth factors and downregulating Rho activity.