RAS in FGF23: another piece in the puzzle.

@article{Ovejero2014RASIF,
  title={RAS in FGF23: another piece in the puzzle.},
  author={Diana Ovejero and Michael T Collins},
  journal={The Journal of clinical endocrinology and metabolism},
  year={2014},
  volume={99 1},
  pages={
          63-6
        }
}
  • D. OvejeroM. Collins
  • Published 2 January 2014
  • Medicine, Biology
  • The Journal of clinical endocrinology and metabolism
The first piece of the puzzle that is the evolving story of fibroblast growth factor-23 (FGF23) physiology was identified in 1959 by Andrea Prader (1). He postulated the existence of a phosphate-regulating hormone as the cause of acquired rickets in a child who was cured by excision of a bone-derived tumor. More pieces were added in 1976, 1989, and 1992, respectively, by the discovery of the Hyp mouse as a model of X-linked hypophosphatemic rickets (XLH) and elegant parabiosis and renal… 
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Keratinocytic epidermal nevi associated with localized fibro‐osseous lesions without hypophosphatemia

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References

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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.

Mechanism of FGF23 processing in fibrous dysplasia

  • N. BhattacharyyaM. Wiench M. Collins
  • Biology, Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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Analysis of blood specimens from patients with FD confirmed that the elevated total FGF23 levels are the result of proportionally increased cF GF23 levels, consistent with less glycosylation and enhanced cleavage by furin, and suggested that FGF 23 processing is a regulated process that controls overall FGF24 activity in FD patients.

Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.

FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, suggesting that this growth factor has a role in phosphate homeostasis.

Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism.

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.

FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa.

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It is shown that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor, and insights into the diversity and specificity of interactions between FGF and FGF receptors are provided.

Regulation of Fibroblast Growth Factor-23 Signaling by Klotho*

It is shown that Klotho protein directly binds to multiple FGF receptors (FGFRs) and significantly enhanced the ability of FGF23 to induce phosphorylation of F GF receptor substrate and ERK in various types of cells.

Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23

A positional cloning approach was used to identify the ADHR gene which included the annotation of 37 genes within 4 Mb of genomic sequence, and missense mutations in a gene encoding a new member of the fibroblast growth factor (FGF) family, FGF23 were identified.

Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice

In vitro iron chelation in vitro resulted in a significant increase in Fgf23 mRNA that was dependent upon Mapk, which supports the concept that late-onset ADHR is the product of gene–environment interactions whereby the combined presence of an FGF23-stabilizing mutation and iron deficiency can lead to ADHR.

Fibroblast growth factor 23: state of the field and future directions