Correlation between metallothionein and matrix metalloproteinase-2 expression and activity in rats during CCl_4-induced hepatic fibrogenesis

AIM:To investigate the relevance between metallothionein(MT) and matrix metalloproteinase-2 (MMP-2) expression and activity in hepatic stellate cells (HSCs). METHODS: Fifty Kunming male mice, weighing 25 g±5 g, were randomly divided into two groups: experiment group (40 mice) and control group (10 mice). CCl4 was used to induce the hepatic fibrosis model in the experiment group. Conditioned medium of HSCs (containing MMP-2) was added at different concentrations of MT, then MMP-2 activity was detected. Liver tissue microarray was used. Collagen fibers was detected by Sirius red staining. The expressions of MMP-2 and MT proteins in liver tissues were detected by immunohistochemistry staining. Gel zymography was used to confirm the activity of MMP-2 in liver tissue homogenate and in the conditioned medium. RESULTS: The expressions of both MMP-2 and MT proteins in liver tissues increased fluctuating with the process of fibrogenesis in the model mice alternately, but the proteins showed out of phase changes. The activity of MMP-2 in the liver tissues also increased gradually and fluctuated with the development of fibrosis. Apart from individual time points, the activity of MMP-2 and MT expression were negatively correlated. The activity of MMP-2 in the conditioned medium treated by MT declined in a dose-dependent manner (r=-0.9990, P0.01). CONCLUSION: The results suggest that there is an upward tendency in the expression of MMP-2 and MT proteins in the liver fibrogenesis, but interaction between them may be exist, and MT inhibits the activity of MMP-2.