Tissue Inhibitor of Metalloproteinase-1 Inhibits Apoptosis of Rat and Human Hepatic Stellate Cells In Vitro

. Liver fibrosis represents the final common pathway for the majority of chronic liver insults (alcohol, autoimmune or viral injury). Current evidence indicates that the central mediator of fibrosis is the hepatic stellate cell (HSC). During fibrotic injury, these retinoid rich cells proliferate and undergo a phenotypic transformation to myofibroblast-like cells, a process termed activation. Previous work by the our group has demonstrated that activated HSC also express the powerful tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, suggesting that matrix degradation is inhibited during fibrogenesis. This hypothesis is supported by findings that spontaneous recovery from liver fibrosis is associated with a diminution of TIMP expression and an increase in collagenase activity with consequent matrix degradation (1). A further finding in this study is that sustained apoptosis of HSC accompanies recovery from fibrosis. This has highlighted the role of TIMP-1 and -2 in HSC proliferation, survival and apoptosis.