title: [Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium].
abstract: Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. Fibroblast growth factor 23 (FGF23) serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into C57BL/6J mice, plasma FGF23 concentration significantly increased. The urinary Pi excretion level was significantly higher in the Cd-injected C57BL/6J mice than in the control group. Plasma Pi concentration decreased only slightly in the Cd-injected mice compared with the control group. No changes were observed in the concentration of the plasma parathyroid hormone and 1,25-dihydroxy vitamin D(3) in both groups of mice. We observed a decrease in phosphate transport activity and also a decrease in the expression level of renal phosphate transporter Npt2c, but not that of Npt2a. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice, which expresses Npt2c as a major NaPi cotransporter. Injecting Cd to Npt2aKO mice induced a significant increase in plasma FGF23 concentration and urinary Pi excretion level. Furthermore, we observed decreases in phosphate transport activity and renal Npt2c expression level in the Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with FGF23.
authors.affiliation: Department of Molecular Nutrition, the University of Tokushima Graduate School, Tokushima, Japan. skido@nutr.med.tokushima-u.ac.jp
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kido
authors.forename: Marina
authors.initials: M
authors.lastname: Fujihara
authors.forename: Kengo
authors.initials: K
authors.lastname: Nomura
authors.forename: Shohei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shiozaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Segawa
authors.forename: Sawako
authors.initials: S
authors.lastname: Tatsumi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism; D002104:Cadmium / Q000009:adverse effects*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D017674:Hypophosphatemia / Q000209:etiology; D007015:Hypophosphatemia, Familial / Q000209:etiology*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010018:Osteomalacia / Q000139:chemically induced / Q000209:etiology; D010710:Phosphates / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; C493555:Slc34a1 protein, mouse; C493563:Slc34a3 protein, mouse; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc; D002104:Cadmium; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23