2015
DOI: 10.1530/joe-15-0225
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FGF23 gene regulation by 1,25-dihydroxyvitamin D: opposing effects in adipocytes and osteocytes

Abstract: In a closed endocrine loop, 1,25-dihydroxyvitamin D3 (1,25D) induces the expression of fibroblast growth factor-23 (FGF23) in bone, with the phosphaturic peptide in turn acting at kidney to feedback repress CYP27B1 and induce CYP24A1 to limit the levels of 1,25D. In 3T3-L1 differentiated adipocytes, 1,25D represses FGF23 and leptin expression, while not affecting leptin receptor transcription, but inducing C/EBP. Conversely, in UMR-106 osteoblast-like cells, FGF23 mRNA concentrations are upregulated by 1,25D, … Show more

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Cited by 50 publications
(42 citation statements)
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“…Interestingly, PTH stimulates Nurr1 expression in osteoblasts prior to FGF-23 elevations and Nurr1 is essential for PTH regulation of FGF-23 gene transcription in UMR-106 osteoblasts [5961]. VDR is known to activate Nurr1 in T-cells [62], raising the possibility that Nurr1 might also mediate the responses to 1,25(OH) 2 D to regulate FGF-23 gene transcription [63]. …”
Section: Fgf-23 Is a Counter-regulatory Hormone For The Pleiotropic Amentioning
confidence: 99%
“…Interestingly, PTH stimulates Nurr1 expression in osteoblasts prior to FGF-23 elevations and Nurr1 is essential for PTH regulation of FGF-23 gene transcription in UMR-106 osteoblasts [5961]. VDR is known to activate Nurr1 in T-cells [62], raising the possibility that Nurr1 might also mediate the responses to 1,25(OH) 2 D to regulate FGF-23 gene transcription [63]. …”
Section: Fgf-23 Is a Counter-regulatory Hormone For The Pleiotropic Amentioning
confidence: 99%
“…There is good evidence that FGF23 is secreted by both osteocytes and osteoblasts in bone [7,8]. Bony FGF23 secretion is stimulated by 1,25(OH) 2 D and by increased extracellular phosphate, thus forming a feedback loop between kidney and bone [5,9,10].…”
Section: Introductionmentioning
confidence: 99%
“…1,25(OH) 2 vitamin D upregulates ETS1, which cooperates with VDR (7,24). An ETS1-VDRE/Nurr1 composite conserved element has recently been defined in the FGF23 proximal promoter (14). The proximity of these elements may allow interactions among the FGFR pathway through ETS1 and Cre, PPR, and PTH action through Nurr1 and VDR through the VDRE/ETS1.…”
Section: Discussionmentioning
confidence: 99%
“…FGF23 expression is also enhanced by 1,25(OH) 2 vitamin D, which binds to a vitamin D-response element (VDRE) in the FGF23 promoter (15). One of the Nurr1 elements at the Ϫ200-to Ϫ399-bp region of the mouse FGF23 promoter is part of a VDRE in the FGF23 promoter (14). This vitamin D receptor (VDR)/Nurr1-element mediates the effect of 1,25(OH) 2 vitamin D and is a cisregulatory module anchored by adjacent ETS1, a transcription factor that cooperates with VDR (4,24), and VDRE/Nurr1 sites (14).…”
mentioning
confidence: 99%
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