Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium

• Aranami Fumito

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Segawa Hiroko

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Furutani Junya

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Kuwahara Shoji

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Tominaga Rieko

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Hanabusa Etsuyo

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Tatsumi Sawako

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Kido Shinsuke

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

• Ito Mikiko

  School of Human Science and Environment, University of Hyogo

• Miyamoto Ken-ichi

  Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School

Abstract

Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis 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 WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D₃ in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis. J. Med. Invest. 57: 95-108, February, 2010

Journal

• The Journal of Medical Investigation

  The Journal of Medical Investigation 57 (1,2), 95-108, 2010

  The University of Tokushima Faculty of Medicine

Keywords

• cadmium
• FGF23
• phosphate
• transporter
• proximal tubule

Details

• CRID: 1390001204243491328
• NII Article ID: 80020865956
• NII Article ID: 130004465206
• NII Book ID: AA11166929
• DOI: 10.2152/jmi.57.95
• ISSN: 13496867
• ISSN: 13431420
• Web Site: http://repo.lib.tokushima-u.ac.jp/77537
• Web Site: http://www.jstage.jst.go.jp/article/jmi/57/1,2/57_1,2_95/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2010325342
• Text Lang: en
• Data Source:
  • JaLC
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed