Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D

Shiguang Liu, Wen Tang, Jianping Zhou, Jason R. Stubbs, Qiang Luo, Min Pi, Leigh Quarles

Research output: Contribution to journalArticle

423 Citations (Scopus)

Abstract

The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 ± 8.1 to 213.8 ± 14.6 pg/ml at 8 h (mean ± SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH)2D3 further increased circulating FGF23 levels. In Gcnt2 null mice, low 1,25(OH)2D3 levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25(OH) 2D3. In osteoblast cell cultures, 1,25(OH) 2D3 but not calcium, phosphate, or parathyroid hormone stimulated FGF23 mRNA levels and resulted in a dose-dependent increase in FGF23 promoter activity. Overexpression of a dominant negative vitamin D receptor inhibited 1,25(OH)2D3 stimulation of FGF23 promoter activity, and mutagenesis of the FGF23 promoter identified a vitamin D-responsive element (-1180 GGAACTcagTAACCT -1156) that is responsible for the vitamin D effects. These data suggest that 1,25(OH)2D3 is an important regulator of FGF23 production by osteoblasts in bone. The physiologic role of FGF23 may be to act as a counterregulatory phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.

Original languageEnglish (US)
Pages (from-to)1305-1315
Number of pages11
JournalJournal of the American Society of Nephrology
Volume17
Issue number5
DOIs
StatePublished - May 1 2006
Externally publishedYes

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Vitamin D
Hormones
Osteoblasts
fibroblast growth factor 23
Familial Hypophosphatemic Rickets
Bone and Bones
Calcitriol Receptors
Calcitriol
Parathyroid Hormone
Mutagenesis
Homeostasis
Cell Culture Techniques
Phosphates
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. / Liu, Shiguang; Tang, Wen; Zhou, Jianping; Stubbs, Jason R.; Luo, Qiang; Pi, Min; Quarles, Leigh.

In: Journal of the American Society of Nephrology, Vol. 17, No. 5, 01.05.2006, p. 1305-1315.

Research output: Contribution to journalArticle

Liu, Shiguang ; Tang, Wen ; Zhou, Jianping ; Stubbs, Jason R. ; Luo, Qiang ; Pi, Min ; Quarles, Leigh. / Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. In: Journal of the American Society of Nephrology. 2006 ; Vol. 17, No. 5. pp. 1305-1315.
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