期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms19071975
关键词
vitamin D receptor; vitamin D; lithocholic acid; bile acid; CYP24A1; TRPV6; calcium metabolism; ileum
资金
- JSPS KAKENHI [JP 22590294, JP 25460394, JP 16K08632, JP 09J0328 (JP21-3828), JP 26860222, JP 16K19062]
The vitamin D receptor (VDR) is a nuclear receptor that mediates the biological action of the active form of vitamin D, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], and regulates calcium and bone metabolism. Lithocholic acid (LCA), which is a secondary bile acid produced by intestinal bacteria, acts as an additional physiological VDR ligand. Despite recent progress, however, the physiological function of the LCA VDR axis remains unclear. In this study, in order to elucidate the differences in VDR action induced by 1,25(OH)(2)D-3 and LCA, we compared their effect on the VDR target gene induction in the intestine of mice. While the oral administration of 1,25(OH)(2)D-3 induced the Cyp24a1 expression effectively in the duodenum and jejunum, the LCA increased target gene expression in the ileum as effectively as 1,25(OH)(2)D-3. 1,25(OH)(2)D-3, but not LCA, increased the expression of the calcium transporter gene Trpv6 in the upper intestine, and increased the plasma calcium levels. Although LCA could induce an ileal Cyp24a1 expression as well as 1,25(OH)(2)D-3, the oral LCA administration was not effective in the VDR target gene induction in the kidney. No effect of LCA on the ileal Cyp24a1 expression was observed in the VDR-null mice. Thus, the results indicate that LCA is a selective VDR ligand acting in the lower intestine, particularly the ileum. LCA may be a signaling molecule, which links intestinal bacteria and host VDR function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据