Biological activity of FGF-23 fragments

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 comp...

Full description

Saved in:
Bibliographic Details
Published in:Pflügers Archiv 2007-07, Vol.454 (4), p.615-623
Main Authors: Berndt, Theresa J, Craig, Theodore A, McCormick, Daniel J, Lanske, Beate, Sitara, Despina, Razzaque, Mohammed S, Pragnell, Marlon, Bowe, Ann E, O'Brien, Stephen P, Schiavi, Susan C, Kumar, Rajiv
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Line
Fibroblast Growth Factors - physiology
Humans
Kidney - cytology
Male
Mice
Mice, Knockout
Molecular Sequence Data
Opossums
Peptide Fragments - physiology
Phosphates - urine
Potassium - blood
Rats
Rats, Sprague-Dawley
Rodents
Vitamin D - analogs & derivatives
Vitamin D - blood
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 1alpha,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.
ISSN:0031-6768
1432-2013
DOI:10.1007/s00424-007-0231-5