Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules

Michel Baum, Susan Schiavi, Vangipuram Dwarakanath, Raymond Quigley

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

Background. Fibroblast growth factor-23 (FGF-23) has been implicated in the renal phosphate wasting in tumor-induced osteomalacia, X-linked hypophosphatemia, and autosomal-dominant hypophosphatemic rickets. Methods. In this in vitro microperfusion study we examined if FGF23R176Q, a stable mutant of FGF-23, impairs phosphate transport in rabbit proximal convoluted and proximal straight tubules perfused in vitro. We also examined if heparin, a molecule that is known to facilitate binding of FGFs to their receptor was necessary for the action of FGF23R176Q on transport. Results. In the presence of heparin, FGF23R176Q reduced phosphate transport from 10.8 ± 2.0 to 9.9 ± 1.9 pmol/mm/min in proximal convoluted tubules and 1.0 ± 0.2 to 0.8 ± 0.2 pmol/mm/min in proximal straight tubules (both P < 0.05). There was no effect of FGF23R176Q in the absence of heparin. Incubation of finely minced mouse renal cortical tissue in tissue culture media for 3 hours resulted in a reduction in brush border membrane vesicles (BBMV) sodium-dependent phosphate transport (NaPi-2A) protein abundance in the presence but not in the absence of heparin. Conclusion. These data demonstrate that the inhibition of phosphate transport by FGF23R176Q in vitro requires heparin. The action of FGF23R176Q is associated with a reduction in BBMV NaPi-2A protein abundance.

Original languageEnglish (US)
Pages (from-to)1148-1153
Number of pages6
JournalKidney international
Volume68
Issue number3
DOIs
StatePublished - Sep 1 2005

Keywords

  • FGF-23
  • Heparin
  • In vitro microperfusion
  • NaPi-2A
  • Rickets
  • Volume absorption

ASJC Scopus subject areas

  • Nephrology

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