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Circulating FGF-23 Is Regulated by 1α,25-Dihydroxyvitamin D3 and Phosphorus in Vivo
- Source :
- Journal of Biological Chemistry. 280:2543-2549
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Fibroblast growth factor-23 (FGF-23), a novel phosphate-regulating factor, was elevated in hypophosphatemic patients with X-linked hypophosphatemic rickets/osteomalacia and also in patients with chronic kidney disease. These observations suggested the pathophysiological importance of FGF-23 on phosphate homeostasis. However, regulation of FGF-23 production is still unclear. We investigated effects of both dietary phosphorus and 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) on circulating FGF-23 in vivo Administration of. 1alpha,25(OH)(2)D(3) dose-dependently increased serum FGF-23 in thyroparathyroidectomized rats without correlating with serum inorganic phosphorus or serum parathyroid hormone. On the other hand, vitamin D receptor null mice had very low serum FGF-23 and did not respond to the 1alpha,25(OH)(2)D(3) administration. These observations suggested 1alpha,25(OH)(2)D(3) directly or indirectly regulates circulating FGF-23. Serum FGF-23 had a strong correlation with serum inorganic phosphorus controlled by dietary phosphorus in 5/6 nephrectomized rats. High phosphate diet elicited a 5-fold increase in serum FGF-23 compared with sham-operated rats, whereas serum FGF-23 did not correlate with serum calcium or serum creatinine in 5/6 nephrectomized rats. Administration of 1alpha,25-dihydroxyvitamin D(3) also elicited a severalfold increase in serum FGF-23 in the uremic rats. Taken together, this shows that both serum phosphorus and 1alpha,25(OH)(2)D(3) regulate circulating FGF-23 independent of each other. Therefore, we proposed there was a feedback loop existing among serum phosphorus, 1alpha,25(OH)(2)D(3), and FGF-23, in which the novel phosphate-regulating bone-kidney axis integrated with the parathyroid hormone-vitamin D(3) axis in regulating phosphate homeostasis.
- Subjects :
- Male
Fibroblast growth factor 23
medicine.medical_specialty
Thyroid Gland
chemistry.chemical_element
Parathyroid hormone
Enzyme-Linked Immunosorbent Assay
Mice, Transgenic
Biochemistry
Calcitriol receptor
Phosphates
Phosphorus metabolism
Rats, Sprague-Dawley
Mice
chemistry.chemical_compound
Calcitriol
Internal medicine
medicine
Animals
Humans
Molecular Biology
Feedback, Physiological
Mice, Knockout
Creatinine
Osteomalacia
Dose-Response Relationship, Drug
Phosphorus
Cell Biology
medicine.disease
Animal Feed
Rats
Fibroblast Growth Factors
Fibroblast Growth Factor-23
Hypophosphatemic Rickets
Endocrinology
Gene Expression Regulation
chemistry
Calcium
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 280
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....afd0d3992d3646c720e2f3713e166695