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

Kidney Int. 2005 Sep;68(3):1148-53. doi: 10.1111/j.1523-1755.2005.00506.x.

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.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Hypophosphatemia / metabolism
  • Hypophosphatemia / physiopathology*
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Phosphates / metabolism*
  • Point Mutation
  • Rabbits
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / metabolism

Substances

  • Phosphates
  • Slc34a1 protein, mouse
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Fibroblast Growth Factors
  • fibroblast growth factor 23