Fibroblast Growth Factor 23: Mechanisms of Action and Regulation

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Toshimi Michigami


                Fibroblast growth factor 23 (FGF23) is a central regulator in mineral metabolism. It is produced mainly by osteocytes in the bone and exerts its effects on distant organs in an endocrine manner. FGF23 generally requires a transmembrane protein named aKlotho to evoke its signal via an FGF receptor (FGFR). In the kidney, FGF23 increases the renal phosphate excretion and decreases the production of 1,25-dihydroxyvitamin D [1,25(OH)2D]. In the parathyroid gland, it suppresses the secretion of parathyroid hormone (PTH). The placenta also expresses both FGFR1 and aKlotho, and an elevated level of maternal FGF23 induces the placental expression of 25-hydroxyvitamin D-24-hydroxylase, affecting fetal vitamin D metabolism. Pathologically elevated levels of FGF23 may exert its effects even on the tissues without aKlotho expression, such as myocardium. Excessive action of FGF23 of various causes leads to hypophosphatemic rickets/osteomalacia, while its impaired action results in hyperphosphatemia and ectopic calcification. Some of the molecules responsible for hereditary hypophosphatemic rickets/osteomalacia reside in the osteocytes and function as local regulators of the production and/or activity of FGF23. The FGF23 expression is controlled by systemic factors also, among which 1,25(OH)2D appears to be a principal regulator. In chronic kidney disease (CKD), FGF23 levels begin to increase from the early stages, although the underlying mechanism still remains unclear. The elevated FGF23 levels in CKD have been shown to be associated with poor outcomes. Elucidation of the mechanism for action and regulation of FGF23 will contribute to the development of new strategies for diagnosis and treatment of the diseases with impaired mineral metabolism. 

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MICHIGAMI, Toshimi. Fibroblast Growth Factor 23: Mechanisms of Action and Regulation. Medical Research Archives, [S.l.], v. 2, n. 5, nov. 2015. ISSN 2375-1924. Available at: <>. Date accessed: 28 may 2018.
FGF23; αKlotho; osteocytes; hypophosphatemic rickets; chronic kidney disease
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