Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations - PubMed (original) (raw)

Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations

Xijie Yu et al. Bone. 2005 Jun.

Abstract

Fibroblast growth factor-23 (FGF23) is a circulating factor that plays critical roles in phosphate and vitamin D metabolism. The goal of our studies was to dissect the pathways directing the vitamin D-phosphate-FGF23 homeostatic axis. To test the role of diet in the regulation of Fgf23, wild-type (WT) mice were fed either a standard (0.44% phosphorus) or a low-phosphate (0.02%) diet. WT mice on standard diet had a serum phosphate of 9.5 +/- 0.3 mg/dl and an Fgf23 concentration of 99.0 +/- 10.6 pg/ml; mice on the low-phosphate diet had a phosphate of 5.0 +/- 0.2 mg/dl (P < 0.01) and an Fgf23 of 10.6 +/- 3.7 pg/ml (P < 0.01). To genetically separate the effects of phosphate and vitamin D on Fgf23, we examined vitamin D receptor null (VDR(-/-)) mice, which are hypocalcemic and hypophosphatemic secondary to hyperparathyroidism. On standard diets, WT and VDR(+/-) mice had Fgf23 levels of 106.0 +/- 30.7 and 90.6 +/- 17.3 pg/ml, respectively, whereas Fgf23 was undetectable in the VDR(-/-). Animals were then placed on a diet that normalizes serum calcium and phosphorus. This 'rescue' increased Fgf23 in WT to 192.3 +/- 32.5 pg/ml and in VDR(+/-) to 388.2 +/- 89.6pg/ml, and importantly, in VDR(-/-) to 476.9 +/- 60.1 pg/ml (P < 0.01 vs. WT). In addition, renal vitamin D 1-alpha hydroxylase (1alpha-OHase) mRNA levels were corrected to WT levels in the VDR(-/-) mice. In summary, Fgf23 is suppressed in diet-induced hypophosphatemia and in hypophosphatemia associated with secondary hyperparathyroidism. Normalization of serum phosphate by diet in VDR(-/-) mice increases Fgf23. Thus, our results demonstrate that Fgf23 is independently regulated by phosphate and by vitamin D.

PubMed Disclaimer

Cited by

FGF23 at the crossroads of phosphate, iron economy and erythropoiesis.
Edmonston D, Wolf M. Edmonston D, et al. Nat Rev Nephrol. 2020 Jan;16(1):7-19. doi: 10.1038/s41581-019-0189-5. Epub 2019 Sep 13. Nat Rev Nephrol. 2020. PMID: 31519999 Review.
FGF23 and Associated Disorders of Phosphate Wasting.
Gohil A, Imel EA. Gohil A, et al. Pediatr Endocrinol Rev. 2019 Sep;17(1):17-34. doi: 10.17458/per.vol17.2019.gi.fgf23anddisordersphosphate. Pediatr Endocrinol Rev. 2019. PMID: 31599133 Free PMC article. Review.
A Novel Distal Enhancer Mediates Inflammation-, PTH-, and Early Onset Murine Kidney Disease-Induced Expression of the Mouse Fgf23 Gene.
Onal M, Carlson AH, Thostenson JD, Benkusky NA, Meyer MB, Lee SM, Pike JW. Onal M, et al. JBMR Plus. 2018 Jan;2(1):32-47. doi: 10.1002/jbm4.10023. Epub 2017 Nov 21. JBMR Plus. 2018. PMID: 29527594 Free PMC article.
The PTH-Vitamin D-FGF23 axis.
Blau JE, Collins MT. Blau JE, et al. Rev Endocr Metab Disord. 2015 Jun;16(2):165-74. doi: 10.1007/s11154-015-9318-z. Rev Endocr Metab Disord. 2015. PMID: 26296372 Review.
Association of vitamin D and FGF23 with serum ferritin in hypoparathyroid thalassemia: a case control study.
Saki F, Salehifar A, Kassaee SR, Omrani GR. Saki F, et al. BMC Nephrol. 2020 Nov 16;21(1):482. doi: 10.1186/s12882-020-02101-3. BMC Nephrol. 2020. PMID: 33198660 Free PMC article.

Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations - PubMed (original) (raw)