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.
Original language | English (US) |
---|---|
Pages (from-to) | 615-623 |
Number of pages | 9 |
Journal | Pflugers Archiv European Journal of Physiology |
Volume | 454 |
Issue number | 4 |
DOIs | |
State | Published - Jul 2007 |
Keywords
- 1α,25(OH)D
- FGF-23
- Kidney
- Phosphate
- Rat
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Physiology (medical)