Hepatic fibrosis reflects hepatotoxin-mediated activation of hepatic stellate cells, resulting in their proliferation and transformation to myofibroblasts that secrete collagen. This activation is suppressed by estrogen, an effect which explains the decreased risk for hepatic fibrosis enjoyed by premenopausal women and by postmenopausal women receiving hormone replacement therapy. Since stellat...

BACKGROUND/AIMS Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypoth...

At the cellular level, the activation and transdifferentiation of quiescent hepatic stellate cells (HSC) into myofibroblasts is the key process involved in hepatic fibrogenesis that is associated with an increased and altered deposition of extracellular matrix components in the liver. The temporal sequence of molecular events associated with stellate cell activation turned out to be appropriate...

The effect of liver growth stimulation [using the rodent PXR (pregnane X receptor) activator PCN (pregnenolone-16alpha-carbonitrile)] in rats chronically treated with carbon tetrachloride to cause repeated hepatocyte necrosis and liver fibrogenesis was examined. PCN did not inhibit the hepatotoxicity of carbon tetrachloride. However, transdifferentiation of hepatic stellate cells and the extent...

The vasculature plays a critical role in multiple physiologic and pathophysiologic processes. A number of recent advances have led to renewed focus on the vasculature in the liver. In patients with chronic liver disease, 3 general vascular beds are of importance. These include the peripheral vasculature, the mesenteric vascular bed, and the intrahepatic microcirculatory unit; abnormalities exis...

Connective tissue growth factor (CTGF/CCN2) regulates cell proliferation, differentiation, adhesion, chemotaxis, migration, apoptosis and extracellular matrix production. Through these diverse actions, CTGF/CCN2 plays a major role in important physiological and pathophysiological processes such as embryogenesis, implantation, angiogenesis, chondrogenesis, tumorigenesis, differentiation, wound h...