Liver fibrosis, the hepatic stellate cell and tissue inhibitors of metalloproteinases

.Liver fibrosis occurs as a consequence of net accumulation of matrix prote ins (especially collagen types I and III) in response to liver injury. The pathogenesis of liver fibrosis is underpinned by the activation of hepatic stellate cells (HSC) to a myofibroblast like phenotype with a consequent in crease in their synthesis of matrix proteins such as interstitial collagens that characterise fibrosis. In addition to this there is increasing eviden ce that liver fibrosis is a dynamic pathologic process in which altered mat rix degradation may also play a major role. Extracellular degradation of ma trix proteins is regulated by matrix metalloproteinases (MMPS) - produced b y HSC - which in turn are regulated by several mechanisms which include reg ulation at the level of the gene (transcription and proenzyme synthesis), c leavage of the proenzyme to an active form and specific inhibition of activ ated forms by tissue inhibitors of metalloproteinases (TIMPS). Insights gai ned into the molecular regulation of HSC activation will lead to therapeuti c approaches in treatment of hepatic fibrosis in the future, and could lead to reduced morbidity and mortality in patients with chronic liver injury.