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 becomes a major effector cell during the development of hepatic fibrosis and cirrhosis. Bile acids may function as costimulatory signalling molecules. This hypothesis was tested in vitro using rat-derived hepatic stellate cells. Bile acids were studied at concentrations that occur during cirrhosis in vivo. Conjugated and unconjugated bile acids rapidly induced egr and fos gene expression as well as cytoplasmic mitogen-activated protein kinase (MAPK) activation. Protein kinase C was required for both egr induction and MAPK activation. These studies imply that bile acids could contribute to the perpetuation of hepatic fibrosis by helping to keep the stellate cell in an activated state.
Brady
L M
LM
Department of Medicine, University of Chicago, IL, USA.
Beno
D W
DW
Davis
B H
BH
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation; D016762:Genes, fos; D017874:Immediate-Early Proteins; D007527:Isoenzymes / Q000378:metabolism; D008095:Lithocholic Acid / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*
D001647:Bile Acids and Salts; D002793:Cholic Acids; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D014157:Transcription Factors; D013656:Taurocholic Acid; D008095:Lithocholic Acid; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019826:Cholic Acid; D013755:Tetradecanoylphorbol Acetate