Nuclear Receptor Regulation of the Adaptive Response of Bile Acid Transporters in Cholestasis

Martin Wagner; Gernot Zollner; Michael Trauner

doi:10.1055/s-0030-1253225

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2010; 30(2): 160-177
DOI: 10.1055/s-0030-1253225

Nuclear Receptor Regulation of the Adaptive Response of Bile Acid Transporters in Cholestasis

Martin Wagner¹ , Gernot Zollner¹ , Michael Trauner¹

¹Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

Abstract

ABSTRACT

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.

KEYWORDS

ABC transporters - bile acids - bilirubin - cholestasis - enterohepatic circulation - multidrug resistance (associated) proteins - nuclear receptors - adaptation

Full Text

References

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Michael TraunerM.D.

Division of Gastroenterology and Hepatology, Department of Internal Medicine

Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria

Email: michael.trauner@meduni-graz.at