Ost , Is Essential for Intestinal Bile Acid Transport and Homeostasis
The organic solute transporter ␣-, Ost␣-Ost, is essential for intestinal bile acid transport and homeostasis Anuradha Rao*, Jamie Haywood*, Ann L. Craddock*, Martin G. Belinsky†, Gary D. Kruh‡, and Paul A. Dawson*§ *Department of Internal Medicine, Section on Gastroenterology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston–Salem, NC 27157; †Medical Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111; and ‡Department of Medicine, Section of Hematology/Oncology, University of Illinois, Chicago, IL 60612 Communicated by David W. Russell, University of Texas Southwestern Medical Center, Dallas, TX, December 28, 2007 (received for review November 28, 2007) The apical sodium-dependent bile acid transporter (Asbt) is respon- Ost␣-Ost efficiently transports the major species of bile acids sible for transport across the intestinal brush border membrane; when expressed in transfected cells (3, 4); and (iv) expression of however, the carrier(s) responsible for basolateral bile acid export Ost␣ and Ost mRNA is positively regulated via the bile into the portal circulation remains to be determined. Although the acid-activated nuclear receptor farnesoid X receptor (FXR) heteromeric organic solute transporter Ost␣-Ost exhibits many (6–9), thereby providing a mechanism to ensure efficient export properties predicted for a candidate intestinal basolateral bile acid of bile acids and protection against their cytotoxic accumulation. transporter, the in vivo functions of Ost␣-Ost have not been Although these data are consistent with a role in bile acid investigated. To determine the role of Ost␣-Ost in intestinal bile transport, the in vivo functions of Ost␣-Ost have not been acid absorption, the Ost␣ gene was disrupted by homologous investigated.
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