| RRC ID |
1941
|
| Author |
Ito M, Sakai Y, Furumoto M, Segawa H, Haito S, Yamanaka S, Nakamura R, Kuwahata M, Miyamoto K.
|
| Title |
Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells.
|
| Journal |
Am J Physiol Endocrinol Metab
|
| Abstract |
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.
|
| Volume |
288(6)
|
| Pages |
E1101-9
|
| Published |
2005-6-1
|
| DOI |
10.1152/ajpendo.00502.2004
|
| PII |
00502.2004
|
| PMID |
15671080
|
| MeSH |
Animals
Base Sequence
Calcitriol / metabolism*
Calcitriol / pharmacology
Cloning, Molecular
DNA / chemistry
DNA / genetics
Fibroblast Growth Factor-23
Fibroblast Growth Factors / chemistry
Fibroblast Growth Factors / genetics
Fibroblast Growth Factors / metabolism*
Humans
K562 Cells
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Phosphates / metabolism*
Phosphates / pharmacology
Polymerase Chain Reaction
Promoter Regions, Genetic
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Receptors, Calcitriol / metabolism
Vitamin D Response Element / physiology
|
| IF |
3.469
|
| Times Cited |
87
|
|
WOS Category
|
PHYSIOLOGY
ENDOCRINOLOGY & METABOLISM
|
| Resource |
| Human and Animal Cells |
Hep G2(RCB1648)
K562(RCB0027)
MC3T3-E1(RCB1126)
RAJI(RCB1647) |
