Vitamin D receptor as an intestinal bile acid sensor

被引：957

作者：

Makishima, M

Lu, TT

Xie, W

Whitfield, GK

Domoto, H

Evans, RM

Haussler, MR

Mangelsdorf, DJ

机构：

[1] Univ Texas, SW Med Ctr, Dept Pharmacol, Howard Hughes Med Inst, Dallas, TX 75390 USA

[2] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, San Diego, CA 92186 USA

[3] Univ Arizona, Coll Med, Dept Biochem & Mol Biophys, Tucson, AZ 85724 USA

来源：

SCIENCE | 2002年 / 296卷 / 5571期

关键词：

D O I：

10.1126/science.1070477

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1alpha-,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. We show that VDR also functions as a receptor for the secondary bile acid lithocholic acid (LCA), which is hepatotoxic and a potential enteric carcinogen. VDR is an order of magnitude more sensitive to LCA and its metabolites than are other nuclear receptors. Activation of VDR by LCA or vitamin D induced expression in vivo of CYP3A, a cytochrome P450 enzyme that detoxifies LCA in the liver and intestine. These studies offer a mechanism that may explain the proposed protective effects of vitamin D and its receptor against colon cancer.

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页码：1313 / 1316

页数：4

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