Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10

• Published in: World journal of gastroenterology : WJG 2005-03, Vol.11 (12), p.1753-1758
• Main Authors: Zheng, Wei-Da, Zhang, Li-Juan, Shi, Mei-Na, Chen, Zhi-Xin, Chen, Yun-Xin, Huang, Yue-Hong, Wang, Xiao-Zhong
• Format: Article
• Language: English
• Subjects: Animals; Basic Research; Carbon Tetrachloride; IL-10; Immunohistochemistry; Interleukin-10 - pharmacology; Liver - metabolism; Liver - pathology; Liver Cirrhosis - drug therapy; Liver Cirrhosis - pathology; Liver Cirrhosis - physiopathology; Male; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; MMP-2; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; TIMP-1; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; 基因表达; 肝星形细胞; 肝纤维化
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v11.i12.1753

AIM: To investigate the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10) .METHODS: Hepatic fibrosis was induced by CCI4 administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCl4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7^th and 11^th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with J3-aclJn signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7th wk, MMP-2 and TIMP-1 mRNA increased in group C (P = 0.001/0.001) and group I (P = 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11^th wk, MMP-2 mRNAin group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P = 0.001), and increased in group C (P = 0.001) while decreased in group I (P = 0.042) compared with that in the 7^th wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.