Regulation of renal phosphate transport by FGF23 is mediated by FGFR1 and FGFR4

Jyothsna Gattineni, Priyatharshini Alphonse, Qiuyu Zhang, Nisha Mathews, Carlton M. Bates, Michel Baum

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that acts on the proximal tubule to decrease phosphate reabsorption and serum levels of 1,25-dihydroxyvitamin D3 [1,25(OH)2 Vitamin D3]. Abnormal FGF23 metabolism has been implicated in several debilitating hypophosphatemic and hyperphosphatemic disorders. The renal receptors responsible for the phosphaturic actions of FGF23 have not been elucidated. There are four fibroblast growth factor receptors (FGFR); 1-4 with "b" and "c" isoforms for receptors 1, 2, and 3. FGFR1, 3, and 4 are expressed in the mouse proximal tubule, and deletion of any one receptor did not affect serum phosphate levels, suggesting that more than one receptor is involved in mediating the phosphaturic actions of FGF23. To determine the receptors responsible for the phosphaturic actions of FGF23, we studied Fgfr1 (kidney conditional) and Fgfr4 (global) double mutant mice (Fgfr1-/-/ Fgfr4-/-). Fgfr1-/-/Fgfr4-/- mice have higher FGF23 levels than their wild-type counterparts (108.1 ± 7.3 vs. 4,953.6 ± 675.0 pg/ml; P < 0.001). Despite the elevated FGF23 levels, Fgfr1-/-/Fgfr4-/- mice have elevated serum phosphorus levels, increased brush-border membrane vesicle (BBMV) phosphate transport, and increased Na-Pi cotransporter 2c (NaPi-2c) protein expression compared with wildtype mice. These data are consistent with FGFR1 and FGFR4 being the critical receptors for the phosphaturic actions of FGF23.

Original languageEnglish (US)
Pages (from-to)F351-F358
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number3
DOIs
StatePublished - Feb 1 2014

Keywords

  • FGF receptors
  • Fibroblast growth factor 23
  • Phosphate
  • Proximal tubule
  • Vitamin D

ASJC Scopus subject areas

  • Physiology
  • Urology

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