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Biological activity of FGF-23 fragments

  • Renal Function, Body Fluids
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

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.

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Acknowledgment

Supported by NIH grant DK-65830, a grant from Genzyme, and the Harvard School of Dental Medicine

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Authors and Affiliations

  1. Department of Internal Medicine, Mayo Clinic College of Medicine, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA

    Theresa J. Berndt, Theodore A. Craig & Rajiv Kumar

  2. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA

    Theresa J. Berndt

  3. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA

    Daniel J. McCormick & Rajiv Kumar

  4. Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave., Boston, MA, 02115, USA

    Beate Lanske, Despina Sitara & Mohammed S. Razzaque

  5. Receptor Ligand Therapeutics, Endocrine and Renal Sciences, Genzyme, 1 Mountain Rd, Framingham, MA, 01701, USA

    Marlon Pragnell, Ann E. Bowe, Stephen P. O’Brien & Susan C. Schiavi

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  1. Theresa J. Berndt
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Correspondence to Rajiv Kumar.

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Berndt, T.J., Craig, T.A., McCormick, D.J. et al. Biological activity of FGF-23 fragments. Pflugers Arch - Eur J Physiol 454, 615–623 (2007). https://doi.org/10.1007/s00424-007-0231-5

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  • DOI: https://doi.org/10.1007/s00424-007-0231-5

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