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http://purl.uniprot.org/citations/15040831http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15040831http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15040831http://www.w3.org/2000/01/rdf-schema#comment"

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We analyzed the effects of an FGF-23 injection in vivo. FGF-23 caused a reduction in serum 1,25-dihydroxyvitamin D by altering the expressions of key enzymes for the vitamin D metabolism followed by hypophosphatemia. This study indicates that FGF-23 is a potent regulator of the vitamin D and phosphate metabolism.

Introduction

The pathophysiological contribution of FGF-23 in hypophosphatemic diseases was supported by animal studies in which the long-term administration of recombinant fibroblast growth factor-23 reproduced hypophosphatemic rickets with a low serum 1,25-dihydroxyvitamin D [1,25(OH)2D] level. However, there is no clear understanding of how FGF-23 causes these changes.

Materials and methods

To elucidate the molecular mechanisms of the FGF-23 function, we investigated the short-term effects of a single administration of recombinant FGF-23 in normal and parathyroidectmized animals.

Results

An injection of recombinant FGF-23 caused a reduction in serum phosphate and 1,25(OH)2D levels. A decrease in serum phosphate was first observed 9 h after the injection and was accompanied with a reduction in renal mRNA and protein levels for the type IIa sodium-phosphate cotransporter (NaPi-2a). There was no increase in the parathyroid hormone (PTH) level throughout the experiment, and hypophosphatemia was reproduced by FGF-23 in parathyroidectomized rats. Before this hypophosphatemic effect, the serum 1,25(OH)2D level had already descended at 3 h and reached the nadir 9 h after the administration. FGF-23 reduced renal mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase and increased that for 25-hydroxyvitamin D-24-hydroxylase starting at 1 h. In addition, an injection of calcitriol into normal mice increased the serum FGF-23 level within 4 h.

Conclusions

FGF-23 regulates NaPi-2a independently of PTH and the serum 1,25(OH)2D level by controlling renal expressions of key enzymes of the vitamin D metabolism. In conclusion, FGF-23 is a potent regulator of phosphate and vitamin D homeostasis."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.org/dc/terms/identifier"doi:10.1359/jbmr.0301264"xsd:string
http://purl.uniprot.org/citations/15040831http://purl.org/dc/terms/identifier"doi:10.1359/jbmr.0301264"xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Fujita T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Fujita T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Yamazaki Y."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Yamazaki Y."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Takeuchi Y."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Takeuchi Y."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Shimada T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Shimada T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Yamashita T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Yamashita T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Fukumoto S."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Fukumoto S."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Nakahara K."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Nakahara K."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Hasegawa H."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Hasegawa H."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Muto T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Muto T."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Hino R."xsd:string
http://purl.uniprot.org/citations/15040831http://purl.uniprot.org/core/author"Hino R."xsd:string
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