HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/G1124    most recent 00539.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (27) Citing Articles via Google Scholar Google Scholar Articles by Boyer, J. L. Articles by Ballatori, N. Search for Related Content PubMed PubMed Citation Articles by Boyer, J. L. Articles by Ballatori, N.

LIVER AND BILIARY TRACT

Upregulation of a basolateral FXR-dependent bile acid efflux transporter OST-OST in cholestasis in humans and rodents

¹Liver Center, Yale University School of Medicine, New Haven, Connecticut; ²Division of Gastroenterology and Hepatology, Department of Medicine, Medical University, Graz, Austria; and the ³Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York

Submitted 28 November 2005 ; accepted in final form 11 January 2006

Organic solute transporter (OST-OST) is a novel heteromeric bile acid and sterol transporter expressed at the basolateral membranes of epithelium in the ileum, kidney, and liver. To determine whether OST-OST undergoes farnesoid X receptor (FXR)-dependent adaptive regulation following cholestatic liver injury, mRNA and protein expression levels were analyzed in patients with primary biliary cirrhosis (PBC) and following common bile duct ligation (CBDL) in rats and Fxr null and wild-type mice. Hepatic OST and OST mRNA increased 3- and 32-fold, respectively, in patients with PBC compared with controls, whereas expression of Ost and Ost also increased in the liver of rats and mice following CBDL. In contrast, expression of Ost and Ost mRNA was generally lower in Fxr null mice, and CBDL failed to enhance expression of Ost and Ost compared with wild-type mice. HepG2 cells treated for 24 h with chenodeoxycholic acid, a selective FXR ligand, had higher levels of OST and OST mRNA and protein. Increases in OST protein were visualized by confocal microscopy at the plasma membrane. These results indicate that expression of Ost and Ost are highly regulated in response to cholestasis and that this response is dependent on the FXR bile acid receptor.

bile acid and steroid transporter; primary biliary cirrhosis; cholangiocytes; kidney; bile acid reabsorption

This article has been cited by other articles:

				O. Renner, S. Harsch, A. Strohmeyer, S. Schimmel, and E. F. Stange Reduced ileal expression of OST{alpha}-OST{beta} in non-obese gallstone disease J. Lipid Res., September 1, 2008; 49(9): 2045 - 2054. [Abstract] [Full Text] [PDF]

				N. Ballatori, F. Fang, W. V. Christian, N. Li, and C. L. Hammond Ost{alpha}-Ost{beta} is required for bile acid and conjugated steroid disposition in the intestine, kidney, and liver Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G179 - G186. [Abstract] [Full Text] [PDF]

				M. G. Donner, S. Schumacher, U. Warskulat, J. Heinemann, and D. Haussinger Obstructive cholestasis induces TNF-{alpha}- and IL-1 -mediated periportal downregulation of Bsep and zonal regulation of Ntcp, Oatp1a4, and Oatp1b2 Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1134 - G1146. [Abstract] [Full Text] [PDF]

				M. Wagner, G. Zollner, P. Fickert, J. Gumhold, D. Silbert, A. Fuchsbichler, J. S. Gujral, K. Zatloukal, H. Denk, H. Jaeschke, et al. Hepatobiliary Transporter Expression in Intercellular Adhesion Molecule 1 Knockout and Fas Receptor-Deficient Mice after Common Bile Duct Ligation Is Independent of the Degree of Inflammation and Oxidative Stress Drug Metab. Dispos., September 1, 2007; 35(9): 1694 - 1699. [Abstract] [Full Text] [PDF]

				S.-Y. Cai, L. Xiong, C. G. Wray, N. Ballatori, and J. L. Boyer The farnesoid X receptor FXR{alpha}/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1400 - R1409. [Abstract] [Full Text] [PDF]

				A.-Q. Sun, N. Balasubramaniyan, K. Xu, C. J. Liu, V. M. Ponamgi, H. Liu, and F. J. Suchy Protein-protein interactions and membrane localization of the human organic solute transporter Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1586 - G1593. [Abstract] [Full Text] [PDF]

				S. J. Keely, M. M. Scharl, L. S. Bertelsen, L. R. Hagey, K. E. Barrett, and A. F. Hofmann Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: structure-activity relationships Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G290 - G297. [Abstract] [Full Text] [PDF]