FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis

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Shimada, Takashi¹; Hasegawa, Hisashi¹; Yamazaki, Yuji¹; Muto, Takanori¹; Hino, Rieko¹; Takeuchi, Yasuhiro²; Fujita, Toshiro²; Nakahara, Kazuhiko³; Fukumoto, Seiji³; Yamashita, Takeyoshi¹

FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis

J Bone Miner Res. March 2004;19(3):429-435

©2004 American Society for Bone and Mineral Research

Affiliations

¹Pharmaceutical Research Laboratories, KIRIN Brewery Co., Ltd., Takasaki, Gunma, Japan

²Department of Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan

³Department of Laboratory Medicine, University of Tokyo Hospital, Bunkyo-ku,Tokyo, Japan
Abstract and keywords

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-1α-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.

Keywords: FGF-23; phosphatonin; phosphate metabolism; vitamin D metabolism; type IIa sodium-phosphate cotransporter
Links

DOI: 10.1359/JBMR.0301264

PubMed: 15040831

WoS: 000189249000011
History

Received: 2003-05-29

Revised: 2003-08-05

Accepted: 2003-10-10

Online: 2003-12-29

Cited By (24)

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