BILE-ACID STIMULATION OF EARLY GROWTH-RESPONSE GENE AND MITOGEN-ACTIVATED PROTEIN-KINASE IS PROTEIN-KINASE C-DEPENDENT

Hepatic stellate cells are exposed to elevated bile acid levels during hepatic injury and fibrogenesis. Upon activation, the stellate cell b ecomes a major effector cell during the development of hepatic fibrosi s and cirrhosis. Bile acids may function as costimulatory signalling m olecules. This hypothesis was tested in vitro using rat-derived hepati c stellate cells. Bile acids were studied at concentrations that occur during cirrhosis in vivo. Conjugated and unconjugated bile acids rapi dly induced egr and fos gene expression as well as cytoplasmic mitogen -activated protein kinase (MAPK) activation. Protein kinase C was requ ired for both egr induction and MAPK activation. These studies imply t hat bile acids could contribute to the perpetuation of hepatic fibrosi s by helping to keep the stellate cell in an activated state.