| First Author | Kim EY | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 4 | PubMed ID | 35216094 |
| Mgi Jnum | J:321595 | Mgi Id | MGI:6886791 |
| Doi | 10.3390/ijms23041980 | Citation | Kim EY, et al. (2022) Transcriptional Control of Trpm6 by the Nuclear Receptor FXR. Int J Mol Sci 23(4) |
| abstractText | Farnesoid x receptor (FXR) is a nuclear bile acid receptor that belongs to the nuclear receptor superfamily. It plays an essential role in bile acid biosynthesis, lipid and glucose metabolism, liver regeneration, and vertical sleeve gastrectomy. A loss of the FXR gene or dysregulations of FXR-mediated gene expression are associated with the development of progressive familial intrahepatic cholestasis, tumorigenesis, inflammation, and diabetes mellitus. Magnesium ion (Mg(2+)) is essential for mammalian physiology. Over 600 enzymes are dependent on Mg(2+) for their activity. Here, we show that the Trpm6 gene encoding a Mg(2+) channel is a direct FXR target gene in the intestinal epithelial cells of mice. FXR expressed in the intestinal epithelial cells is absolutely required for sustaining a basal expression of intestinal Trpm6 that can be robustly induced by the treatment of GW4064, a synthetic FXR agonist. Analysis of FXR ChIP-seq data revealed that intron regions of Trpm6 contain two prominent FXR binding peaks. Among them, the proximal peak from the transcription start site contains a functional inverted repeat 1 (IR1) response element that directly binds to the FXR-RXRalpha heterodimer. Based on these results, we proposed that an intestinal FXR-TRPM6 axis may link a bile acid signaling to Mg(2+) homeostasis. |
