Role of fibroblast growth factor 23 in health and in chronic kidney disease

@article{Fukagawa2005RoleOF,
  title={Role of fibroblast growth factor 23 in health and in chronic kidney disease},
  author={Masafumi Fukagawa and Tomoko Nii-Kono and Junichiro J Kazama},
  journal={Current Opinion in Nephrology and Hypertension},
  year={2005},
  volume={14},
  pages={325–329}
}
Purpose of reviewThis review summarizes the molecular properties and biological roles of a new phosphaturic factor, fibroblast growth factor 23 (FGF23). Significant roles of FGF23 are discussed, especially in terms of its effects on the kidney, the main target organ. Recent findingsFGF 23 is a recently discovered phosphaturic factor. Several animal experiments including overexpression or ablation of the FGF23 gene have recently revealed the significant effects of this factor on phosphate… 
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References

SHOWING 1-10 OF 58 REFERENCES
Targeted ablation of Fgf 23 demonstrates an essential physiological role of FGF 23 in phosphate and vitamin D metabolism
TLDR
Evidence is presented that FGF 23 is a physiological regulator of serum phosphate and 1,25dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice, indicating that F GF23 is essential for normal phosphate and vitamin D metabolism.
Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism.
TLDR
Evidence is presented that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF 23-null mice, indicating that F GF23 is essential for normal phosphate and vitamin D metabolism.
Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders.
TLDR
The findings strongly support the novel concept that high circulating levels of FGF23 are associated with profound disturbances in the regulation of phosphate and vitamin D metabolism as well as calcium homeostasis and that elevated PTH levels likely also contribute to the renal phosphate wasting associated with these disorders.
Fibroblast Growth Factor (FGF)-23 Inhibits Renal Phosphate Reabsorption by Activation of the Mitogen-activated Protein Kinase Pathway*
TLDR
The present findings have revealed a novel MAPK-dependent mechanism of the regulation of phosphate uptake by FGF signaling, which was found to require heparin-like molecules for its inhibitory activity on phosphate uptake.
Circulating FGF-23 Is Regulated by 1α,25-Dihydroxyvitamin D3 and Phosphorus in Vivo*
TLDR
There was a feedback loop existing among serum phosphorus, 1α,25(OH)2D3, and FGF-23, in which the novel phosphate-regulating bone-kidney axis integrated with the parathyroid hormone-vitamin D3 axis in regulating phosphate homeostasis.
FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting.
TLDR
It is found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro and may play an important role in the renal phosphate-wasting syndrome associated with FD/MAS.
FGF-23 is elevated by chronic hyperphosphatemia.
TLDR
Serum FGF-23 levels are elevated in patients with hyperphosphatemia and chronic hypoparathyroidism, suggesting a feedback system in which serum F GF-23 responds to serum phosphorus and regulates it, as well as circumventing the confounding effect of serum PTH and calcium.
The phosphatonin pathway: new insights in phosphate homeostasis.
TLDR
A new class of phosphate-regulating factors, collectively known as the phosphatonins, have been shown to be associated with the hypophosphatemic diseases, tumor-induced osteomalacia (TIO), X-linked hypoph phosphate-linked rickets (XLH), and autosomal-dominant hypoph phosphatemic rickets and their role under normal or pathologic conditions is not yet clear.
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