New molecular insights into the mechanisms of cholestasis.
Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibility and disease progression in acquired cholestatic disorders. Cholestasis is associated with complex transcriptional and post-transcriptional alterations of hepatobiliary transporters and enzymes participating in bile formation. Ligand-activated nuclear receptors for bile acids and other biliary compounds play a key role in the regulation of genes required for bile formation. Pharmacological interventions in cholestasis may aim at modulating such novel regulatory pathways. This review will summarize the principles of molecular alterations in cholestasis and will give an overview of potential clinical implications.
Wagner
Martin
M
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Laboratory of Experimental and Molecular Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Zollner
Gernot
G
Trauner
Michael
M
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D001646:Bile / Q000378:metabolism*; D002779:Cholestasis / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D026901:Membrane Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear