title: Apoptotic and survival signals in hepatic stellate cells.
abstract: Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis. In response to liver injury, HSCs undergo a process called activation, which involves 2 steps jonit nation from quiescent phenotype to myofibroblast-like phenotype, and perpetuation that maintains the activated phenotype of HSCs. The fate of the activated HSCs depends on the apoptotic and survival signals that they receive. The apoptosis of HSCs results from a series of complex and interrelated signaling events. Apoptotic signals for the activated HSCs include proteins from membrane receptors, such as death receptors, nerve growth factor receptor and peripheral-type benzodiazepine receptor, as well as proteins from cytoplasm such as Bcl-2 family members. The survival signals for the activated HSCs are induced by some kinases and cytokines including tissue inhibitors of metalloproteinase-1, Rho/Rho kinase, platelet-derived growth factor, transforming growth factor beta-1, and insulin-like growth factor-1. Approaches that specifically initiate HSC apoptosis are promising to be direct and effective strategies to treat liver fibrosis. Although it remains unclear whether the activated HSCs could be reversed back to the quiescent phenotype, the different expression and sensitivity of pro-apoptotic and survival molecules between quiescent and activated HSCs provide a prospect to develop therapeutic approaches that specifically targets apoptosis of the activated HSCs. These therapeutic strategies to induce HSC apoptosis are current research hotspot and the future for the patients with liver fibrosis and cirrhosis.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Jianghong
authors.initials: J
authors.lastname: Fan
authors.forename: Gerald
authors.initials: G
authors.lastname: Minuk
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
mesh_terms: D017209:Apoptosis; D002470:Cell Survival; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction