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The Roles of Fibroblast Growth Factor (FGF)-23, α-Klotho and Furin Protease in Calcium and Phosphate Homeostasis : A Mini-Review

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Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

The roles of calcitonin, parathormone and calcitriol in the regulation of plasma calcium and phosphate are well-established. However, in autosomal-dominant hypophosphatemic rickety patients, studies have revealed normal plasma levels of calcium, associated with normal thyroid and parathyroid functions, but decreased levels of phosphate and calcitriol despite adequate reserves of vitamin D. Also, in tumoral calcinosis, persistent hyperphosphatemia with increased levels of 1,25(OH)2D3 have been observed. These studies indicate the involvement of factors other than the ones already known. The first decade of this century/millennium has led to the discovery of the involvement of fibroblast growth factor-23, furin protease and α-klotho in the homeostasis of calcium and phosphate, which is the subject of this mini-review.

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References

  1. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22:6267–76.

    Article  CAS  PubMed  Google Scholar 

  2. Perwad F, Azam N, Zhang MYH, Yamashita T, Tenenhouse HS, Portale AA. Dietary and serum phosphorus regulate fibroblast growth factor-23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology. 2005;146:5358–64.

    Article  CAS  PubMed  Google Scholar 

  3. Kida Y, Fukumoto S, Yamashita T, Jonsson K, Econs M, Juppner H. Fibroblast growth factor-23 in oncogenic osteomalacia and X-linked hypophosphatemia. New Engl J Med. 2003;349:505–6.

    Article  PubMed  Google Scholar 

  4. Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Lunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Juppner H. Fibroblast growth factor-23 in oncogenic osteomalacia and X-linked hypophosphatemia. New Engl J Med. 2003;348:1656–63.

    Article  CAS  PubMed  Google Scholar 

  5. Rodriguez M, Lopez I, Munoz J, Aguilera-Tejero E, Almaden Y. FGF23 and mineral metabolism, implications in CKD-MBD. Nefroligia. 2012;32(3):275–8.

    Google Scholar 

  6. Larson T, Davis SI, Garringer HJ, Mooney SD, Draman MS, Cullen MJ, White KE. Fibroblast growth factor-23 mutants causing familial tumoral calcinosis are differentially processed. Endocrinology. 2005;146:3883–91.

    Article  Google Scholar 

  7. Bergwitz C, Banerjee S, Abu-Zahra H, Kaji H, Miyauchi A, Sugimoto T, Juppner H. Defective O-glycosylation due to a novel homozygous S129P mutation is associated with lack of fibroblast growth factor-23 secretion and tumoral calcinosis. J Clin Endocrinol Metab. 2009;94(11):4267–74.

    Article  CAS  PubMed  Google Scholar 

  8. Nabeshima Y. Regulation of calcium homeostasis. Clin Calcium. 2010;20(11):1677–85.

    CAS  PubMed  Google Scholar 

  9. Antonuicci DM, Yamashita T, Portale AA. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab. 2006;91:3144–9.

    Article  Google Scholar 

  10. Ubaidus S, Li M, Sultana S, de Freitas PHL, Oda K, Maeda T, Takagi R, Amizuka N. FGF-23 is mainly synthesized by osteocytes in the regularly distributed osteocytic lacunar canalicular system established after physiological bone remodeling. J Electron Microsc (Tokyo). 2009;58:381–92.

    Article  CAS  Google Scholar 

  11. Liu S, Quarles LD. How fibroblast growth factor-23 works. J Am Soc Nephrol. 2007;18(6):1637–47.

    Article  CAS  PubMed  Google Scholar 

  12. Perward F, Zhang MYH, Tenehouse HS, Portale. Fibroblast growth factor-23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxy vitamin D 1-α hydroxylase expression in vitro. Am J Renal Physiol. 2007;293:1577–83.

    Article  Google Scholar 

  13. White KE, Larsson TE, Econs MJ. The roles of specific genes implicated as circulating factors involved in normal and disordered phosphate homeostasis: frizzled related protein-4, matrix extracellular phosphoglyco- protein and fibroblast growth factor-23. Endocrinol Rev. 2006;27:221–41.

    Article  CAS  Google Scholar 

  14. Gattineni J, Bates C, Twombley K, Dwarkanath V, Robinson ML, Goetz R, Mohammadi M, Baum M. FGF-23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF-receptor-1. Am J Physiol Renal Physiol. 2009;297:F282–91.

    Article  CAS  PubMed  Google Scholar 

  15. Ramon I, Kleynen P, Body JJ, Karmali R. Fibroblast growth factor-23 and its role in phosphate homeostasis. Eur J Endocrinol. 2010;162:1–10.

    Article  CAS  PubMed  Google Scholar 

  16. Masi L, Gozzini A, Franchi A, Companacci D, Amedei A, Falchetti A, Franceschelli F, Marcucci G, Tanini A, Capanna R, Brandi ML. A novel recessive mutation of fibroblast growth factor-23 in tumoral calcinosis. J Bone Joint Surg. 2009;91:1190–8.

    Article  CAS  PubMed  Google Scholar 

  17. Nabeshima Y. Discovery of α-klotho and FGF-23 unveiled new insight into calcium and phosphate homeostasis. Clin Calcium. 2008;18(7):923–34.

    CAS  PubMed  Google Scholar 

  18. Razzaque MS, Lanske B. The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis. J Endocrinol. 2007;194:1–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. de Groot T, van der Hagen EA, Verkaart S, Te Boekhorst VA, Bindels RJ, Hoenderop JG. The role of the TRPV5 N-terminus in channel activity, tetramerization and trafficking. J Biol Chem. 2011;286(37):32132–9.

    Article  PubMed  Google Scholar 

  20. Urakawa L, Yamazak Y, Shimada T, Lijima K, Haseqawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. Klotho converts FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770–4.

    Article  CAS  PubMed  Google Scholar 

  21. Wise RJ, Barr PJ, Wong PA, Kiefer MC, Brake AJ, Kaufman RJ. Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. Proc Natl Acad Sci USA. 1991;87(23):9378–82.

    Article  Google Scholar 

  22. Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 2002;3(10):753–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Conflict of Interest

Since this is a single author review article and involving no experimental work, research funding or support, I certify that there is no conflict with anyone in this regard.

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Correspondence to Roshan L. Mattoo.

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Mattoo, R.L. The Roles of Fibroblast Growth Factor (FGF)-23, α-Klotho and Furin Protease in Calcium and Phosphate Homeostasis : A Mini-Review. Ind J Clin Biochem 29, 8–12 (2014). https://doi.org/10.1007/s12291-013-0324-1

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  • DOI: https://doi.org/10.1007/s12291-013-0324-1

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