Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells.
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.
Ito
Mikiko
M
Department of Molecular Nutrition, Institute of Health Biosciences, The Univ. of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima, Japan.
Sakai
Yuko
Y
Furumoto
Mari
M
Segawa
Hiroko
H
Haito
Sakiko
S
Yamanaka
Setsuko
S
Nakamura
Rie
R
Kuwahata
Masashi
M
Miyamoto
Ken-ichi
K
D000818:Animals; D001483:Base Sequence; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010710:Phosphates / Q000378:metabolism* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018167:Receptors, Calcitriol / Q000378:metabolism; D030181:Vitamin D Response Element / Q000502:physiology
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D004247:DNA; D002117:Calcitriol