期刊
SEMINARS IN LIVER DISEASE
卷 30, 期 2, 页码 178-185出版社
THIEME MEDICAL PUBL INC
DOI: 10.1055/s-0030-1253226
关键词
Bile acid homeostasis; ileal bile acid transporter; adaptive regulation; nuclear receptor
资金
- NIDDK NIH HHS [R37 DK025636, P30 DK034989] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK034989, R37DK025636] Funding Source: NIH RePORTER
Organic solute transporter alpha-beta (OST alpha-OST beta) is a unique heteromeric transporter localized to the basolateral membrane of epithelial cells involved in sterol transport. It is believed to be the primary bile acid efflux transporter in the intestine of mammals and is therefore essential to bile acid homeostasis and the enterohepatic circulation. First described in the evolutionarily primitive small skate, Leucoraja erinacea, this facilitated transporter requires expression of both subunits for its function. It can transport a variety of bile acids, as well as estrone 3-sulfate, dehydroepiandrosterone 3-sulfate, digoxin, and prostaglandin E(2). Expression of both subunits is variable between species and tissues; in humans high expression is noted in the liver, small intestine, kidney, testis, and adrenal gland. OST alpha-OST beta is directly regulated by the bile acid sensing nuclear receptor, farnesoid X receptor (FXR). Furthermore, it is part of the complex regulatory pathway that controls bile acid synthesis and homeostasis. Hepatic OST alpha-OST beta is upregulated in cholestasis in both humans and rodents, where it appears to play a protective role. Additional studies are necessary to determine its role in liver injury, bile acid malabsorption, and lipid and glucose metabolism, as well as a potential protective role for kidney OST alpha-OST beta in cholestasis.
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