{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:07:43Z","timestamp":1790665663942,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1012090, 2016R1C1B2009587, 2017M3A9G8083382, 2019R1H1A1101394, 2021R1A5A2021614"],"award-info":[{"award-number":["2020R1C1C1012090, 2016R1C1B2009587, 2017M3A9G8083382, 2019R1H1A1101394, 2021R1A5A2021614"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (Mg2+) is essential for mammalian physiology. Over 600 enzymes are dependent on Mg2+ for their activity. Here, we show that the Trpm6 gene encoding a Mg2+ 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-RXR\u03b1 heterodimer. Based on these results, we proposed that an intestinal FXR-TRPM6 axis may link a bile acid signaling to Mg2+ homeostasis.<\/jats:p>","DOI":"10.3390\/ijms23041980","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T02:35:51Z","timestamp":1644546951000},"page":"1980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcriptional Control of Trpm6 by the Nuclear Receptor FXR"],"prefix":"10.3390","volume":"23","author":[{"given":"Eun Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-5136","authenticated-orcid":false,"given":"Jae Man","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"BK21 FOUR KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"ref_1","first-page":"72","article-title":"Isolation of proteins that interact specifically with the retinoid X receptor: Two novel orphan receptors","volume":"9","author":"Seol","year":"1995","journal-title":"Mol. 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