Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Zollner, G; Fickert, P; Fuchsbichler, A; Silbert, D; Wagner, M; Arbeiter, S; Gonzalez, FJ; Marschall, HU; Zatloukal, K; Denk, H; Trauner, M.
Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine.
J Hepatol. 2003; 39(4):480-488
Doi: 10.1016/S0168-8278(03)00228-9
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- Führende Autor*innen der Med Uni Graz
- Trauner Michael
- Zollner Gernot
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Fickert Peter
- Silbert-Wagner Dagmar
- Wagner Martin
- Zatloukal Kurt
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- Abstract:
- Background/Aims: Adaptive changes in transporter expression in liver and kidney provide alternative excretory pathways for biliary constituents during cholestasis and may thus attenuate liver injury. Whether adaptive changes in ATP-binding cassette (ABC) transporter expression are stimulated by bile acids and their nuclear receptor FXR is unknown.Methods: Hepatic, renal and intestinal ABC transporter expression was compared in cholic acid (CA)- and ursodeoxycholic acid (UDCA)-fed wild-type (FXR+/+) and FXR knock-out mice (FXR-/-). Expression was assessed by reverse transcription-polymerase chain reaction, immunoblotting and immunofluorescence microscopy.Results: CA feeding stimulated hepatic Mrp2, Mrp3, Bsep and renal Mrp2 as well as intestinal Mrp2 and Mrp3 expression. Lack of Bsep induction by CA in FXR-/- was associated with disseminated hepatocyte necrosis which was not prevented by compensatory induction of Mrp2 and Mrp3. With the exception of Bsep, UDCA stimulated expression of hepatic, renal and intestinal ABC transporters independent of FXR without inducing liver toxicity.Conclusions: Toxic CA and non-toxic UDCA induce adaptive ABC transporter expression, independent of FXR with the exception of Bsep. Stimulation of hepatic Mrp3 as well as intestinal and renal Mrp2 by UDCA may contribute to its therapeutic effects by inducing alternative excretory routes for bile acids and other cholephiles. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- ATP-Binding Cassette Transporters - metabolism
- Adaptation, Physiological -
- Animals -
- Cell Nucleus - metabolism
- Cholic Acid - pharmacology Cholic Acid - physiology
- DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology
- Intestines - metabolism
- Kidney - metabolism
- Liver - drug effects Liver - metabolism Liver - pathology
- Membrane Transport Proteins - metabolism
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout - genetics
- Multidrug Resistance-Associated Proteins - metabolism
- Receptors, Cytoplasmic and Nuclear - physiology
- Transcription Factors - genetics Transcription Factors - physiology
- Up-Regulation -
- Ursodeoxycholic Acid - pharmacology Ursodeoxycholic Acid - physiology
- Find related publications in this database (Keywords)
- bile acid
- cholestasis
- orphan nuclear receptor
- transcription factor