Gene regulation in hepatic stellate cell.
Hepatic stellate cells are now recognized as the major source of extracellular matrix in hepatic fibrosis. Following liver injury the hepatic stellate cell changes from a quiescent to an activated cell. The activation process includes an increased proliferation rate, a phenotypic change to a myofibroblast-like cell, loss of vitamin A stores, increased extra-cellular matrix protein synthesis and contractility. Furthermore, hepatic stellate cells have been implicated in hepatic inflammation through their ability to secrete cytokines and chemokines. Here, we review the literature on the molecular pathogenesis of hepatic stellate cells activation with emphasis on the most recent findings. The reviewed topics include transcriptional and post-transcriptional regulation of the genes encoding type I collagen in hepatic stellate cells; the role of the transcription factor nuclear factor Kappa B in the hepatic stellate cell activation; focal adhesion kinase and integrin-mediated signal transduction in hepatic stellate cell, and apoptosis in hepatic stellate cells. New insight into hepatic stellate cell activation and death may lead to the development of novel therapies for hepatic fibrosis.
Lang
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University of North Carolina at Chapel Hill, Department of Medicine, Chapel Hill, USA.
Brenner
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DA
D017209:Apoptosis; D002455:Cell Division; D003094:Collagen / Q000235:genetics; D005109:Extracellular Matrix / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction
D003094:Collagen