Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells.

Ito M, Sakai Y, Furumoto M, Segawa H, Haito S, Yamanaka S, Nakamura R, Kuwahata M, Miyamoto K

Department of Molecular Nutrition, Institute of Health Biosciences, The Univ. of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima, Japan.

Fibroblast growth factor-23 (FGF-23) has been recently identified as playing an important pathophysiological role in phosphate homeostasis and vitamin D metabolism. To elucidate the precise physiological regulation of FGF-23, we characterized the mouse FGF-23 5'-flanking region and analyzed its promoter activity. The 5'-flanking region of the mouse FGF-23 gene contained a TFIID site (TATA box) and several putative transcription factor binding sites, including MZF1, GATA-1 and c-Ets-1 motifs, but it did not contain the typical sequences of the vitamin D response element. Plasmids encoding 554-bp (pGL/-0.6), 364-bp (pGL/-0.4) and 200-bp (pGL/-0.13) promoter regions containing the TFIID element and +1-bp fragments drove the downstream expression of a luciferase reporter gene in transfection assays. We also found that FGF-23 mRNA was expressed in K-562 erythroleukemia cell lines but not in MC3T3-E1, Raji, or Hep G2 human carcinoma cells. Treatment with 1,25-dihydroxyvitamin D3 in the presence of high phosphate markedly stimulated pGL/-0.6 activity, but calcium had no effect. In addition, the plasma FGF-23 levels were affected by the dietary and plasma inorganic phosphate concentrations. Finally, the levels of plasma FGF-23 in vitamin D receptor-null mice were significantly lower than in wild-type mice. The presents study demonstrated that vitamin D and the plasma phosphate level are important regulators of the transcription of the mouse FGF-23 gene.

Published 10 May 2005 in Am J Physiol Endocrinol Metab, 288(6): E1101-9.
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