Bile acid stimulation of early growth response gene and mitogen-activated protein kinase is protein kinase C-dependent
- Resource Type
- Authors
- David W.A. Beno; Bernard H. Davis; Lynda Brady
- Source
- Biochemical Journal. 316:765-769
- Subject
- Male
Taurocholic Acid
medicine.medical_specialty
Transcription, Genetic
Liver cytology
medicine.drug_class
Cholic Acid
Biology
Biochemistry
Immediate-Early Proteins
Bile Acids and Salts
Rats, Sprague-Dawley
chemistry.chemical_compound
Internal medicine
medicine
Animals
Protein kinase A
Molecular Biology
Cells, Cultured
Protein Kinase C
Protein kinase C
Early Growth Response Protein 1
Bile acid
Cholic acid
Genes, fos
Cholic Acids
Cell Biology
G protein-coupled bile acid receptor
Rats
Cell biology
DNA-Binding Proteins
Enzyme Activation
Isoenzymes
Endocrinology
Liver
chemistry
Calcium-Calmodulin-Dependent Protein Kinases
Hepatic stellate cell
Tetradecanoylphorbol Acetate
Lithocholic Acid
Hepatic fibrosis
Transcription Factors
Research Article
- Language
- ISSN
- 1470-8728
0264-6021
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 co-stimulatory 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.