Nuclear receptor regulation of the adaptive response of bile acid transporters in cholestasis.
Although hereditary or acquired defects in hepatobiliary transporter systems cause or predispose to cholestasis, adaptive bile acid transporter changes can counteract cholestasis by reducing hepatocellular and systemic concentrations of retained cholephiles. An important level in the regulation of adaptive bile acid transporters and overflow pathways is mediated at the transcriptional level by nuclear hormone receptors. Moreover, therapeutic approaches targeting nuclear receptors in cholestasis may stimulate these adaptive changes and open a new perspective for the treatment of cholestatic liver diseases. This review gives a comprehensive overview on bile acid transporters in the enterohepatic circulation and their adaptive changes in response to cholestasis as well as the regulatory networks underlying these adaptive mechanisms.
Wagner
Martin
M
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Zollner
Gernot
G
Trauner
Michael
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology; D000222:Adaptation, Physiological; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D002779:Cholestasis / Q000503:physiopathology*; D000090702:Constitutive Androstane Receptor; D004764:Enterohepatic Circulation / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D047493:PPAR alpha / Q000819:agonists / Q000502:physiology; D000077297:Pregnane X Receptor; D018167:Receptors, Calcitriol / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000502:physiology; D011987:Receptors, Steroid / Q000502:physiology; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000502:physiology; D000099150:Receptor, Farnesoid X-Activated
D018435:ATP Binding Cassette Transporter, Subfamily B; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D000090702:Constitutive Androstane Receptor; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; D047493:PPAR alpha; D000077297:Pregnane X Receptor; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; D000099150:Receptor, Farnesoid X-Activated; C082631:NR5A2 protein, human; C000607071:RARA protein, human; C037643:bile acid binding proteins; C099713:nuclear receptor subfamily 0, group B, member 2