title: Mechanisms of liver fibrosis.
abstract: Liver fibrosis represents a significant health problem worldwide of which no acceptable therapy exists. The most characteristic feature of liver fibrosis is excess deposition of type I collagen. A great deal of research has been performed to understand the molecular mechanisms responsible for the development of liver fibrosis. The activated hepatic stellate cell (HSC) is the primary cell type responsible for the excess production of collagen. Following a fibrogenic stimulus, HSCs change from a quiescent to an activated, collagen-producing cell. Numerous changes in gene expression are associated with HSC activation including the induction of several intracellular signaling cascades, which help maintain the activated phenotype and control the fibrogenic and proliferative state of the cell. Detailed analyses in understanding the molecular basis of collagen gene regulation have revealed a complex process offering the opportunity for multiple potential therapeutic strategies. However, further research is still needed to gain a better understanding of HSC activation and how this cell maintains its fibrogenic nature. In this review we describe many of the molecular events that occur following HSC activation and collagen gene regulation that contribute to the fibrogenic nature of these cells and provide a review of therapeutic strategies to treat this disease.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, NC 27599-7032, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tsukada
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Parsons
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rippe
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D020869:Gene Expression Profiling; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D008954:Models, Biological; D008517:Phytotherapy; D015398:Signal Transduction
chemical_list: D000975:Antioxidants