Fibroblast growth factor 23 enhances renal klotho abundance
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Klotho constitutes the receptor for fibroblast growth factor 23 (FGF23). However, the effects of FGF23 on renal and circulating klotho are not well-known. In vivo experiments were performed to assess the effects of FGF23 (10 μg/kg), parathyroid hormone (PTH, 10 μg/kg), and 1,25-dihydroxy-vitamin D3 (1,25VD, 1 μg/kg) on renal expression and serum concentration of klotho in Wistar rats. Phosphate excretion was increased at 3 h after FGF23 administration (p < 0.05). Renal klotho expressions and serum klotho levels were elevated at 3 h (p < 0.01) by FGF23. At 24 h, phosphate excretion was still elevated (p < 0.05), and serum phosphate, 1,25VD, and PTH were reduced (p < 0.05). However, serum and renal klotho returned to the control level at 24 h. PTH markedly increased phosphate excretion after 24 h (p < 0.01). There were increases in FGF23 at 3 and 24 h, and 1,25VD at 24 h after PTH administration (p < 0.05). Serum klotho concentration and renal klotho expression were elevated by PTH at 3 or 24 h. After 24 h of exposure to 1,25VD, considerable increases in serum FGF23, calcium, and phosphate were seen (p < 0.05), but PTH was decreased (p < 0.01). 1,25 VD elevated renal klotho expression and serum klotho (p < 0.05) at 3 h, but returned to control levels at 24 h. Our data indicate that FGF23 rapidly increases renal klotho expression and serum klotho. The present findings are consistent with the notion that PTH increases phosphate excretion at least in part through elevations of FGF23 and klotho. Moreover, our results suggest that 1,25VD increases klotho expression independently of FGF23.
KeywordsEarly growth response-1 transcriptional factor Parathyroid hormone Phosphaturia 1,25-Dihydroxy-vitamin D3 25-Hydroxyvitamin D-1 alpha-hydroxylase
The authors have no conflicts of interest to declare regarding this paper. This study was partly supported by the grant from Saitama Medical University (no. 20-1-2-07). No additional external funding was received for this study. The authors thank Ms. Makiko Funabashi, Makiko Sato for the technical assistance. We appreciate Mr. Masayoshi Okubo and Katsumi Ogiwara for taking care of the animals. Parts of the data in this manuscript were presented in the annual meeting of the American Society of Nephrology in San Diego CA USA, October 2009.
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