Pflügers Archiv - European Journal of Physiology

, Volume 454, Issue 4, pp 615–623

Biological activity of FGF-23 fragments

Authors

  • Theresa J. Berndt
    • Department of Internal MedicineMayo Clinic College of Medicine, Mayo Clinic Rochester
    • Department of Physiology and Biomedical EngineeringMayo Clinic College of Medicine, Mayo Clinic Rochester
  • Theodore A. Craig
    • Department of Internal MedicineMayo Clinic College of Medicine, Mayo Clinic Rochester
  • Daniel J. McCormick
    • Department of Biochemistry and Molecular BiologyMayo Clinic College of Medicine, Mayo Clinic Rochester
  • Beate Lanske
    • Department of Developmental BiologyHarvard School of Dental Medicine
  • Despina Sitara
    • Department of Developmental BiologyHarvard School of Dental Medicine
  • Mohammed S. Razzaque
    • Department of Developmental BiologyHarvard School of Dental Medicine
  • Marlon Pragnell
    • Receptor Ligand Therapeutics, Endocrine and Renal SciencesGenzyme
  • Ann E. Bowe
    • Receptor Ligand Therapeutics, Endocrine and Renal SciencesGenzyme
  • Stephen P. O’Brien
    • Receptor Ligand Therapeutics, Endocrine and Renal SciencesGenzyme
  • Susan C. Schiavi
    • Receptor Ligand Therapeutics, Endocrine and Renal SciencesGenzyme
    • Department of Internal MedicineMayo Clinic College of Medicine, Mayo Clinic Rochester
    • Department of Biochemistry and Molecular BiologyMayo Clinic College of Medicine, Mayo Clinic Rochester
Renal Function, Body Fluids

DOI: 10.1007/s00424-007-0231-5

Cite this article as:
Berndt, T.J., Craig, T.A., McCormick, D.J. et al. Pflugers Arch - Eur J Physiol (2007) 454: 615. doi:10.1007/s00424-007-0231-5

Abstract

The phosphaturic activity of intact, full-length, fibroblast growth factor-23 (FGF-23) is well documented. FGF-23 circulates as the intact protein and as fragments generated as the result of proteolysis of the full-length protein. To assess whether short fragments of FGF-23 are phosphaturic, we compared the effect of acute, equimolar infusions of full-length FGF-23 and various FGF-23 fragments carboxyl-terminal to amino acid 176. In rats, intravenous infusions of full-length FGF-23 and FGF-23 176–251 significantly and equivalently increased fractional phosphate excretion (FE Pi) from 14 ± 3 to 32 ± 5% and 15 ± 2 to 33 ± 2% (p < 0.001), respectively. Chronic administration of FGF-23 176–251 reduced serum Pi and serum concentrations of 1α,25-dihydroxyvitamin D. Shorter forms of FGF-23 (FGF-23 180–251 and FGF-23 184–251) retained phosphaturic activity. Further shortening of the FGF-23 carboxyl-terminal domain, however, abolished phosphaturic activity, as infusion of FGF-23 206–251 did not increase urinary phosphate excretion. Infusion of a short fragment of the FGF-23 molecule, FGF-23 180–205, significantly increased FE Pi in rats and reduced serum Pi in hyperphosphatemic Fgf-23−/− knockout mice. The activity of FGF-23 180–251 was confirmed in opossum kidney cells in which the peptide reduced Na+-dependent Pi uptake and enhanced internalization of the Na+-Pi IIa co-transporter. We conclude that carboxyl terminal fragments of FGF-23 are phosphaturic and that a short, 26-amino acid fragment of FGF-23 retains significant phosphaturic activity.

Keywords

FGF-23RatPhosphateKidney1α,25(OH)2D

Copyright information

© Springer-Verlag 2007