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Identification of the molecules which regulate the phosphate signaling network in mammalian kidney

Research Project

Project/Area Number 12470211
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 Ken-ichi  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (70174208)

Co-Investigator(Kenkyū-buntansha) KUWAHATA Masashi  The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 助手 (30304512)
ITOH Mikiko  The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 助手 (50314852)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥11,400,000 (Direct Cost: ¥11,400,000)
KeywordsPhosphate sensor / Phosphate transporter / FGF23 / Kidney / Hyperphosphatemia / リン酸 / PHEX / 腎機能 / キイロショウジョウバエ / プロテアーゼ / 液性因子 / 骨代謝
Research Abstract

The kidney plays a major role in maintaining proper serum phosphate concentrations through mechanisms that are not completely understood. The identification of genes causing rare, heritable disorders of impaired phosphate regulation provides an opportunity to discover novel renal pathways that control mineral ion balance. We recently identified the gene causing ADHR as FGF23, which encodes a novel, secreted protein that shares 25 to 35 % homology with the fibroblast growth factor (FGF) family. However, the molecular targets of FGF23 is unknown. Several mammalian renal Na^+ -dependent Pi cotranspoters have recently been isolated and characterized. The cDNAs of these transporters can be divided into three types (types I-III) in the kidney cortex. It has been demonstrated that the type II transporter is a major functional Na^+ -dependent Pi cotransporter in the proximal tubules.
In the present study, we identified a molecular target of FGF23. This protein is a mammalian Na/Pi-cotransporter with a high degree of homology to described type II Na/Pi-cotransporters. Expression of the mRNA and the protein of such a transport protein was demonstrated in the mammalian kidney. Kinetic properties and pH dependence of type IIc-mediated Na/Pi-cotransport favor this protein as a candidate for a Na/Pi cotransporter involved in renal Pi transport.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Arai H.: "The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene"J Bone Miner Res. 16. 1256-1264 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyamoto K.: "Transcriptional regulation of the NPT2 gene by dietary phosphate"Kindney Int.. 60. 412-415 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nii T.: "Dietary demonstration of humorally mediated inhibition of the transcription of phosphate transpoter in XLH patients"Clin Exp Nephrol.. 5. 144-152 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nii T.: "Molecular events involved in up.regulating human Na+-independent neural amino acid transporter LAT1 during T-cell activation"Biochem J.. 358. 396-704 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai,H., Miyamoto,K., Yoshida,M., Yamamoto,H., Taketani,Y., Morita,K., Kubota,M., Yoshida,S., Ikeda,M., Watabe,F., Kanemasa,Y., Takeda,E.: "The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human D receptor gene"J Bone Miner Res. 16 (7). 1256-1264 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyamoto,K., Ito,M.: "Transcriptional regulation of the NPT2 gene by dietary phosphate"Kidney Int.. 60 (2). 412-415 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nii,T., Taketani,Y., Tani,Y., Ohkido,I., Segawa,H., Yamamoto,H., Morita,K., Minamitani,K., Minagawa,M., Yasuda,T., Niimi,H., Miyauchi,A., Miyamoto,K., Takeda,E.: "Dietary demonstration of humorally mediated inhibition of the transcription of phosphate transpoter in XLH patients"Clin Exp Nephrol. 5. 144-152 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nii,T., Segawa,H., Taketani,Y., Tani,Y., Ohkido,I., Kishida,S., Ito,M., Endou,H., Kanai,Y., Takeda,E., Miyamoto,K.: "Molecular eveents involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation"Biochem J.. 358. 693-704 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai H.: "The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene"J Bone Miner Res. 16. 1256-1264 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamoto K.: "Transcriptional regulation of the NPT2 gene by dietary phosphate"Kidney Int.. 60. 412-415 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nii T.: "Dietary demonstration of humorally mediated inhibition of the transcription of phosphate transpoter in XLH patients"Clin Exp Nephrol.. 5. 144-152 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nii T.: "Molecular events involved in up-regulating human Na^+-independent neural amino acid transporter LAT1 during T-cell activation"Biochem J.. 358. 693-704 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uemura H.: "Close correlation between estrogen treatment and renal phosphate reabsorption capacity"J.Clinic.Endoc.Metab.. 85. 1215-1219 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanai Y.: "Transport properties of a system y+L neutral and basic amino acid transporter : Insights into the mechanisms of substrate recognition."J.Biol.Chem.. 275. 20787-20793 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto K.: "Identification and function analysis of three isoforms for the Na+-dependent co-transporter (NaPi-2) in rat kidney."Nephrol.Dial.Transplant.. 15. 31-33 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto K.: "Secondary hyperparathyroidism and phosphate sensing in parathyroid glands."J.Med.Invest.. 47. 118-122 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeda E.: "Molecular mechanisms of mammalian inorganic phosphate homeostasis."Advan.Enzyme.Regul.. 40. 285-302 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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