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Review
. 2010 Apr;25(4):591-601.
doi: 10.1007/s00467-009-1273-z. Epub 2009 Aug 11.

Regulation of phosphate transport by fibroblast growth factor 23 (FGF23): implications for disorders of phosphate metabolism

Jyothsna Gattineni  1 , Michel Baum
Affiliations
Review

Regulation of phosphate transport by fibroblast growth factor 23 (FGF23): implications for disorders of phosphate metabolism (V体育官网入口)

"V体育平台登录" Jyothsna Gattineni et al. Pediatr Nephrol. 2010 Apr.

Abstract

There are a number of hypophosphatemic disorders due to renal phosphate wasting that cannot be explained by elevated levels of parathyroid hormone. The circulating factors responsible for the phosphaturia have been designated as phosphatonins. Studies of patients with tumor-induced osteomalacia and other genetic diseases of phosphate metabolism have resulted in the identification of a number of hormones that regulate phosphate homeostasis, including matrix extracellular phosphoglycoprotein (MEPE), secreted frizzled-related protein 4 (sFRP-4), dentin matrix protein 1 (DMP1), fibroblast growth factor 7 (FGF7), fibroblast growth factor 23 (FGF23), and Klotho. Our understanding of the actions of these hypophosphatemic peptides has been enhanced by studies in mice either overexpressing or not expressing these hormones. This review focuses on FGF23 since its regulation is disordered in diseases that affect children, such as X-linked hypophosphatemia, autosomal dominant and recessive hypophosphatemic rickets as well as chronic kidney disease. Recent studies have shown that FGF23 is unique among the FGFs in its requirement for Klotho for receptor activation. Here, we also discuss new potentially clinically important data pointing to the receptor(s) that mediate the binding and action of FGF23 and Klotho. VSports手机版.

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Figures

Fig. 1
Fig. 1
Fibroblast growth factor 23 (FGF23)–kidney–gastrointestinal tract–parathyroid axis. This figure demonstrates the complex interaction between the various hormones that play a role in phosphate homeostasis. FGF23 is primarily produced in the bone, which decreases the expression of an electrogenic phosphate transporter (sodium-dependent phosphate transporter 2a, NaPi-2a) and an electro-neutral phosphate transporter (NaPi-2c) on the apical surface of the proximal tubule, causing phosphaturia. FGF23 also decreases the serum levels of 1,25(OH)2 vitamin D3. Decreased 1,25(OH)2 vitamin D3 levels in turn decreases the gastrointestinal absorption of phosphorus. 1,25(OH)2 Vitamin D3 stimulates FGF23 production, which in turn decreases 1,25(OH)2 vitamin D3. FGF23 directly or indirectly decreases NaPi-2b expression in the small intestine. Serum parathyroid hormone (PTH) stimulates the synthesis of 1,25(OH)2 vitamin D3, which in turn decreases PTH levels as a negative feedback mechanism. PTH also decreases NaPi-2a and NaPi-2c expression. FGF23 decreases PTH secretion. The solid lines indicate positive regulation, and the dotted lines indicate negative regulation
Fig. 2
Fig. 2
FGF23–Klotho binding to the FGF receptor and schematic representation of the actions of FGF23 in the proximal tubular cell. This figure shows the interaction between the FGF receptor (FGFR), FGF23, Klotho, and heparin on the surface of the cell. FGF23 binds to the FGFR–Klotho complex with heparin stabilizing this complex. Activation of FGFR results in the activation of intracellular signaling pathways, which in turn decreases the expression of NaPi-2a, NaPi-2c, and 1α-hydroxylase. This results in decreased phosphate absorption from the proximal tubule and decreased synthesis of 1,25(OH)2 vitamin D3
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References

    1. Forster IC, Hernando N, Biber J, Murer H. Proximal tubular handling of phosphate: A molecular perspective. Kidney Int. 2006;70:1548–1559. - PubMed
    1. Levi M, Lotscher M, Sorribas V, Custer M, Arar M, Kaissling B, Murer H, Biber J. Cellular mechanisms of acute and chronic adaptation of rat renal P(I) transporter to alterations in dietary P(I) Am J Physiol. 1994;267:F900–F908. - PubMed
    1. Murer H, Forster I, Hernando N, Lambert G, Traebert M, Biber J. Posttranscriptional regulation of the proximal tubule NaPi-II transporter in response to PTH and dietary P(I) Am J Physiol. 1999;277:F676–F684. - VSports app下载 - PubMed
    1. Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I, Tatsumi S, Miyamoto K. Growth-related renal type II Na/Pi cotransporter. J Biol Chem. 2002;277:19665–19672. - VSports注册入口 - PubMed
    1. Segawa H, Yamanaka S, Ito M, Kuwahata M, Shono M, Yamamoto T, Miyamoto K. Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet. Am J Physiol Renal Physiol. 2005;288:F587–F596. - "V体育官网" PubMed

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