TY - JOUR
T1 - Regulation of phosphate transport by fibroblast growth factor 23 (FGF23)
T2 - Implications for disorders of phosphate metabolism
AU - Gattineni, Jyothsna
AU - Baum, Michel
N1 - Funding Information:
This work was supported by NIH grants DK41612, DK065842, and DK078596 to M.B, T32 DK07257 (Peter Igarashi and M.B.), and the O’Brien Center P30DK079328 (Peter Igarashi, PI).
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Hypophosphatemia
KW - Klotho
KW - Proximal tubule
KW - Sodium phosphate cotransporter
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U2 - 10.1007/s00467-009-1273-z
DO - 10.1007/s00467-009-1273-z
M3 - Article
C2 - 19669798
AN - SCOPUS:77951259224
SN - 0931-041X
VL - 25
SP - 591
EP - 601
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 4
ER -