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Fibroblast growth factor 23 in renal phosphate reabsorption and vitamin D metabolism

Research Project

Project/Area Number 14370320
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

MIYAMOTO Kenichi  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (70174208)

Co-Investigator(Kenkyū-buntansha) SEGAWA Hiroko  The University of Tokushima, School of Medicine, Assistant professor, 医学部, 助手 (70325257)
ITHO Mikiko  The University of Tokushima, School of Medicine, Assistant professor, 医学部, 助手 (50314852)
KUWAHATA Masashi  The University of Tokushima, School of Medicine, Associate professor, 医学部, 講師 (30304512)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥11,500,000 (Direct Cost: ¥11,500,000)
KeywordsFGF23 / phosphate / kidney / phosphatonin / receptor / Brain
Research Abstract

Fibroblast growth factor 23 (FGF23), a phosphaturic factor, is involved in the regulation of renal Pi reabsocption. Proteolysis-resistant FGF23 mutants expressed in rodents reduce Pi uptake in both intestine and kidney, independent of parathyroid hormone action. In the present study, we investigated whether FGF23 affect dietary regulation of Na^+-dependent Pi (Na/Pi) cotransport in rat kidney using wild-type FGF23 and an R 179Q mutant, which disrupts a consensus proteolytic cleavage motif
Rats injected with naked human FGF23 DNA (wild type or R 179Q mutant) expressed human FGF23 transcript in the liver. In those animals, the plasma calcium and parathyroid hormone levels were not affected by FGF23 (either wild type or R179Q mutant). FGF23-R179Q did, however, significantly decrease the plasma Pi and renal Na/Pi cotransport activity and also the levels of type IIc Na/Pi cotransporter proteins in BBMVs from normal rat kidney. In rats fed a low Pi diet, the levels of type IIa and type IIc Na/Pi cotransporters were markedly ink in Western blotting and immunohistochemical analyses. After injection of FGF23-R 179Q DNA into the rats fed a low Pi diet, the levels of the type IIa and type IIc transporter proteins were decreased. Thus FGF23 mutant blunts the signaling of Pi deprivation in renal type II Na/Pi cotransporters, suggesting that the FGF23 pathway could be involved in the signaling of dietary Pi

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Saito H. et al.: "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1α, 25-dihydroxyvitamin D3 production."J Biol Chem. 278. 2206-2011 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Taketani.Y.et al.: "Increase in IP3 and intracellular Ca2+ induced by phosphate depletion LLC-PK1 cells."Biochemical and Biophyssical Reserch Communnications. 305. 287-291 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyamoto K. et al.: "Molecular targets of hyperphosphataemia in chronic renal failure."Nephrol Dial Transplant. 18. 79-80 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Segawa H. et al.: "Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter."Pflugers Arch-Eur J Physiol. 446. 585-592 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohkido I. et al.: "Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney."Pflugers Arch-Eur J Physiol. 446. 106-115 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N.: "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1 α, 25dihydroxyvitamin D3 production"J Biol Chem. 278. 2206-2211 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Taketani.Y, Nomoto M, Yamamoto H, Isshiki M, Morita K, Arai H, Miyamoto K, Kato S, Takeda E: "Increase in IP3 and intracellular Ca2+ induced by phosphate depletion LLC-PK1 cells"Biochemical and Biophysical Research Communications. 305. 287-291 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyamoto K, Ito M, segawa H, Kuwahata M.: "Molecular targets of hyperphosphataemia in chronic renal failure"Nephrol Dial Transplant. 18[Suppl 3]. iii79-iii80 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Segawa H, Kawakami E, Kaneko I, Kuwahata M, Ito M, Kusano K, Saito H, Fukushima N, Miyamoto K.: "Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter"Pflugers Arch-Eur J Physiol. 446. 585-592 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohkido I, Segawa H, Yanagida R, Nakamura M, Miyamoto K.: "Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney"Pflugers Arch.2003 Apr. 446(1). 106-115 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito H.et al.: "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1α,25-dihydroxyvitamin D3 production"J Biol Chem. 278. 2206-2011 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taketani.Y.et al.: "Increase in IP3 and intracellular Ca2+ induced by phosphate depletion LLC-PK1 cells"Biochemical and Biophyssical Reserch Communnications. 305. 287-291 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyamoto K.et al.: "Molecular targets of hyperphosphataemia in chronic renal failure"Nephrol Dial Transplant. 18. 79-80 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Segawa H.et al.: "Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter"Pflugers Arch-Eur J Physiol. 446. 585-592 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohkido I.et al.: "Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney"Pflugers Arch-Eur J Physiol. 446. 106-115 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Segawa H.: "Growth-related renal type II Na/Pi contransporter"J Biol Chem. 277. 19665-19672 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda E.: "Phosphorus supply per capita from food in Japan between 1960 and 1995"Journal of Nutrition Science and Vitaminology. 48. 102-108 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 桑波田 雅士: "生体の無機リン酸感受機構"腎と骨代謝. 15. 27-32 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 伊藤 美紀子: "無機リン酸トランスポーターファミリー"Annual Review 腎臓. 22-26 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮本 賢一: "臨床とのかかわり-血中カルシウム・リン濃度調節の理解はどう進歩したか?"腎と骨代謝. 15. 317-322 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito H: "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1α, 25-dihydroxyvitamin D3 production"J Biol Chem. 278. 2206-2211 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 桑波田 雅士: "リン代謝の最近の理解とリン調節薬の将来、透析療法ネクストII透析骨症は防げる"43-48 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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