Volume 27, Issue 11 (October 2017)
Japanese

Update on recent progress in vitamin D research. Vitamin D receptor and the nuclear receptor superfamily. Makishima Makoto 1 1Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan. pp.1533-1541
Published Date 2017/10/28
DOI https://doi.org/10.20837/4201711025
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 The vitamin D receptor(VDR)is a ligand-dependent transcription factor of the nuclear receptor superfamily. VDR belongs to the NR1I subfamily along with other nuclear receptors involved in xenobiotic metabolism, such as pregnane X receptor. The oxysterol receptors liver X receptors α/β and the bile acid receptor farnesoid X receptor belong to the NR1H subfamily, which are closely related to the NR1I subfamily. NR1I and NR1H nuclear receptors form heterodimers with retinoid X receptor. The active form of vitamin D, 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], acts as a physiological VDR ligand, and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity, and cardiovascular function. The secondary bile acid lithocholic acid, which is produced by intestinal bacteria, is another natural VDR ligand. Lithocholic acid stimulates xenobiotic metabolism and regulates immune and inflammatory responses via VDR, and its calcemic action is limited and observed only in vitamin D-deficient animals. Thus, lithocholic acid may be a function-selective VDR ligand. VDR is a promising drug in the treatment of bone and mineral disorders, cancer, autoimmune disease, inflammation, and cardiovascular disease. However, the adverse effect hypercalcemia limits wider clinical application of 1,25(OH)2D3 and its derivatives. Elucidation of the mechanism of VDR function by lithocholic acid should expand the possibility of VDR-targeted approaches.



基本情報

09175857.27.11.jpg
CLINICAL CALCIUM
27巻11号 (2017年10月)
電子版ISSN 印刷版ISSN 0917-5857 医薬ジャーナル社

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