Tissue inhibitor of metalloproteinase-1 and -2 RNA expression in rat and human liver fibrosis.

摘要: The remodeling of extracellular matrix during chronic liver disease may partially be attributed to altered activity metalloproteinases and their tissue inhibitors (TIMPs). Expression TIMP-1 -2 was studied by in situ hybridization combined with immunohistochemistry rat (acute carbon tetrachloride intoxication secondary biliary fibrosis) human livers on isolated hepatic stellate cells. transcripts appeared within 1 3 hours after intoxication, pointing a role the protection against accidental activation metalloproteinases, were present at high levels all fibrotic predominantly TIMP-2 RNA distribution largely matched previously reported patterns metalloproteinase-2 (72-kd gelatinase) expression, suggesting generation TIMP-2/matrix complex (large inhibitor metalloproteinases). Isolated cells expressed RNA. Addition transforming growth factor-beta enhanced vitro, whereas TIMP-2-specific signals reduced, likely result stoichiometric excess matrix-metalloproteinase-2 over TIMP-2. In context previous demonstrations vivo, these suggest an intrahepatic environment permitting only limited degradation, ultimately resulting redistribution relative accumulation collagen type 1.