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Regulation of Fibroblast Growth Factor 23 by Iron, EPO, and HIF

  • Molecular Control of Phosphorus Homeostasis (B van der Eerden, Section Editor)
  • Published:
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Abstract

Purpose of Review

Fibroblast growth factor-23 (FGF23) is the key hormone produced in bone critical for phosphate homeostasis. Elevated serum phosphorus and 1,25-dihydroxyvitamin D stimulates FGF23 production to promote renal phosphate excretion and decrease 1,25-dihydroxyvitamin D synthesis, thus completing the feedback loop and suppressing FGF23. Unexpectedly, studies of common and rare heritable disorders of phosphate handling identified links between iron and FGF23 demonstrating novel regulation outside the phosphate pathway.

Recent Findings

Iron deficiency combined with an FGF23 cleavage mutation was found to induce the autosomal dominant hypophosphatemic rickets phenotype. Physiological responses to iron deficiency, such as erythropoietin production as well as hypoxia inducible factor activation, have been indicated in regulating FGF23. Additionally, specific iron formulations, used to treat iron deficiency, alter post-translational processing thereby shifting FGF23 protein secretion.

Summary

Molecular and clinical studies revealed that iron deficiency, through several mechanisms, alters FGF23 at the transcriptional and post-translational level. This review will focus upon the novel discoveries elucidated between iron, its regulators, and their influence on FGF23 bioactivity.

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Funding

The authors would like to acknowledge NIH grants F32-AR065389 (ELC); the Comprehensive Training Program in Musculoskeletal Research Grant T32-AR065971 (JAW) and a Center for Translational Sciences Institutional Biomedical Research Grant (ELC).

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Authors and Affiliations

  1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, 635 Barnhill Drive, MS5055P, Indianapolis, IN, 46202, USA

    Jonathan A. Wheeler & Erica L. Clinkenbeard

  2. Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut St., IB130, Indianapolis, IN, 46202, USA

    Erica L. Clinkenbeard

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  1. Jonathan A. Wheeler
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Correspondence to Erica L. Clinkenbeard.

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Jonathan A. Wheeler and Erica L. Clinkenbeard each declare no potential conflicts of interest.

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This article is part of the Topical Collection on Molecular Control of Phosphorus Homeostasis

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Wheeler, J.A., Clinkenbeard, E.L. Regulation of Fibroblast Growth Factor 23 by Iron, EPO, and HIF. Curr Mol Bio Rep 5, 8–17 (2019). https://doi.org/10.1007/s40610-019-0110-9

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