title: Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters.
abstract: Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. The mechanisms for elevated BA levels are poorly understood in both clinical and experimental studies. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the BA-synthesizing enzyme Cyp7a1 and the BA transporters Ntcp, Bsep, Mrp3, Ost-α, and Ost-β. Sprague-Dawley rats were randomized to the CRF group (&frac56; nephrectomy) or to the sham-operated control group and were analyzed 8 wk after surgery. Results obtained in the CRF rats were compared with those obtained in rats that had undergone uninephrectomy (UNX). The CRF group exhibited significantly increased plasma cholesterol and BA concentrations. Hepatic Cyp7a1 mRNA and protein levels were almost identical in the two groups. Hepatic Mrp3, Ost-α, and Ost-β expression was increased, suggesting increased basolateral efflux of bile acids into the blood. However, no such changes in BA transporter expression were observed in the remnant kidney. In UNX rats, similar changes in plasma BA levels and in the expression of BA transporters were found. We hypothesize that the increase in plasma BA is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane.
authors.affiliation: Dept. of Clinical Pharmacology and Toxicology, Univ. Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland. gerd.kullak@usz.ch.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Gai
authors.forename: Lei
authors.initials: L
authors.lastname: Chu
authors.forename: Christian
authors.initials: C
authors.lastname: Hiller
authors.forename: Denis
authors.initials: D
authors.lastname: Arsenijevic
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Penno
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Montani
authors.forename: Alex
authors.initials: A
authors.lastname: Odermatt
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C037643:bile acid binding proteins
keywords: bile acid transporter; chronic renal failure; liver