Hepatic stellate cell - myofibroblast transition: cellular basis for the pathogenesis of liver fibrosis.

Liver fibrosis is the result of chronic liver damage, it is characterized by excessive accumulation of connective tissue. In healthy liver, hepatic stellate cels: and to a lesser extent parenchymal and endothelial cells, are responsible for intrahepatic connective tissue synthesis. Under pathological conditions, stellate cells transdifferentiate into myofibroblast-like cells that proliferate and secrete large quantities of connective tissue. Within the general theme of our research group the following subjects are currently investigated: 1) suppresion of stellate cell - myofibroblast transition by histon deacetylase inhibitors, 2) role of histone deacetylase (HDAC) inhibitors, 2) role of histone deacetylases in transdifferentiation of hepatic stellate cells, 3) role of RAR/RXR and PPAR nuclear receptors in stellate cel transdiffernetiation, 4) function of H2O2 in regulation of the autocrine TGF-B-loop, 5) function of intermediate filament proteins desmin, GFAP and nestin in stellate cells, 6) induction of portal hypertension by contraction of activated stellate cells. Projects 3,4 en 5 were funded by OZR grant nr. 196332120.