Liver fibrosis: signals leading to the amplification of the fibrogenic hepatic stellate cell.
Liver fibrosis represents a major medical problem with significant morbidity and mortality. Worldwide hepatitis viral infections represent the major cause liver fibrosis; however, within the United States chronic ethanol consumption is the leading cause of hepatic fibrosis. Other known stimuli for liver fibrosis include helminthic infection, iron or copper overload and biliary obstruction. Fibrosis can be classified as a wound healing response to a variety of chronic stimuli that is characterized by an excessive deposition of extracellular matrix proteins of which type I collagen predominates. This excess deposition of extracellular matrix proteins disrupts the normal architecture of the liver resulting in pathophysiological damage to the organ. If left untreated fibrosis can progress to liver cirrhosis ultimately leading to organ failure and death if left untreated. This review will discuss the molecular events leading to liver fibrosis. The discussion will include collagen gene regulation and proliferative signals that contribute to the amplification of the hepatic stellate cell, the primary fibrogenic cell type that resides in the liver.
Gäbele
Erwin
E
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Brenner
David A
DA
Rippe
Richard A
RA
D000818:Animals; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*