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


CONCLUSIONS
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.
Baum
Michel
M
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9063, USA. Michel.Baum@UTSouthwestern.edu
Schiavi
Susan
S
Dwarakanath
Vangipuram
V
Quigley
Raymond
R
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D017674:Hypophosphatemia / Q000378:metabolism / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000378:metabolism*; D017354:Point Mutation; D011817:Rabbits; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism
C000717428:Fgf23 protein, mouse; D010710:Phosphates; C493555:Slc34a1 protein, mouse; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23