Regulation of vitamin D metabolizing enzymes in murine renal and extrarenal tissues by dietary phosphate, FGF23, and 1,25(OH)2D3

PloS One
Larissa KägiCarsten A Wagner

Abstract

The 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) together with parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) regulates calcium (Ca2+) and phosphate (Pi) homeostasis, 1,25(OH)2D3 synthesis is mediated by hydroxylases of the cytochrome P450 (Cyp) family. Vitamin D is first modified in the liver by the 25-hydroxylases CYP2R1 and CYP27A1 and further activated in the kidney by the 1α-hydroxylase CYP27B1, while the renal 24-hydroxylase CYP24A1 catalyzes the first step of its inactivation. While the kidney is the main organ responsible for circulating levels of active 1,25(OH)2D3, other organs also express some of these enzymes. Their regulation, however, has been studied less. Here we investigated the effect of several Pi-regulating factors including dietary Pi, PTH and FGF23 on the expression of the vitamin D hydroxylases and the vitamin D receptor VDR in renal and extrarenal tissues of mice. We found that with the exception of Cyp24a1, all the other analyzed mRNAs show a wide tissue distribution. High dietary Pi mainly upregulated the hepatic expression of Cyp27a1 and Cyp2r1 without changing plasma 1,25(OH)2D3. FGF23 failed to regulate the expression of any of the studied hydroxylases at the used dosage and treatment ...Continue Reading

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Citations

Sep 16, 2018·Nature Reviews. Endocrinology·Sampada Chande, Clemens Bergwitz
Sep 27, 2019·PloS One·Vidyanand AnapartiHani El-Gabalawy
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Jun 13, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rocío FuenteIsabel Rubio-Aliaga

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Methods Mentioned

BETA
Assay
ELISA
PCR
Protein Assay

Software Mentioned

Quantitiy One
GraphPad Prism

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