Dual Expression of Matrix Metalloproteinase-2 and Membrane- Type 1-Matrix Metalloproteinase in Fibrotic Human Livers

作者: T Takahara , K Furui , Y Yata , B Jin , L P Zhang

DOI: 10.1002/HEP.510260620

关键词: PathologyMatrix metalloproteinaseFibrosisMolecular biologyMatrix (biology)Hepatic stellate cellGene expressionCirrhosisBiologyEndoplasmic reticulumIn situ hybridization

摘要: We have previously reported increased expression of matrix metalloproteinase-2 (MMP-2) using a rat model liver fibrosis. However we did not clarify how the precursor MMP-2 (proMMP-2) was activated. Therefore, used human specimens with chronic hepatitis (CH) and cirrhosis (LC) to examine membrane-type-1-MMP (MT1-MMP), which has recently been determined activate proMMP-2. Northern hybridization studies showed 5.4- 1.4- fold increase in CH LC, respectively, as compared normal liver. MT1-MMP gene simultaneously 4.0- 1.4-fold respectively. In situ 35S-cRNA probes prominent silver granules elongated cells found lobules, periportal areas, fibrous septa LC samples. These expressed alpha-smooth muscle actin by immunohistochemistry. Immunoelectron microscopic examination localized rough endoplasmic reticulum stellate located lobules or fibroblasts septa, suggesting that were produced these cells. addition, cytoplasmic membranous immunodeposits both MMPs endothelial cells, Kupffer capillary lymphocytes, indicating activation proMMP-2 occurs locally. Increased detected while dual over-expression fibroblasts, possibly resulting active around findings suggest activated may remodel parenchyma during process (Hepatology 1997 Dec;26(6):1521-9)

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