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BIOCHEMICAL AND HISTOCHEMICAL EXAMINATIONS ON LIPJD-BINDING PROTEINS (LBP), PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS (PPAR) AND RETINOL RECEPTORS (RXR) IN KIDNEY.

Research Project

Project/Area Number 12671034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionFACULTY OF MEDICINE FUKUI MEDICAL UNIVERSITY

Principal Investigator

KIMURA Hideki  FUKUI MEDICAL UNIVERSITY, FACULTY OF MEDICINE, ASSISTANT, 附属病院, 助手 (20283187)

Co-Investigator(Kenkyū-buntansha) FUJII Hiroshi  NIGATA UNIVERSITY,FACULTY OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助教授 (90165340)
SUZUKI Satoru  FUKUI MEDICAL UNIVERSITY,FACULTY OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助教授 (00206484)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordskidnev / PPAR / Hold-binding nrotein / cell culture / PAI- 1 / GETP / eosmophil / homocvsteine / Immuno histochemistry / Macrophage / Homocysteine
Research Abstract

1. Investigation on the expression ofLBPs and PPARs in normal and diseased human kidneys.
(1) In normal human kidney, liver type (L-) fatty acid-binding protein (FABP) and heart-type FABP were predominantly localized in cytoplasm of proximal and distal renal tubular epithelial cells (RTEC), respectively. PPAR-α was mainly present in cytoplasm of proximal RTEC and PPAR-γ was present in cytoplasm of distal RTEC and collecting ducts.
(2) As for transplanted kidneys suffering from severe hypoxia, the expressions of L-FABP and PPAR-α were increased in cytoplasm of some proximal RTECs. In interstitial nephritis, nuclear stainings for L-FABP and PPAR-α were found in some proximal RTECs, suggesting the interaction between L-FABP and PPAR-α. Purified L-FABP contained endogenously long-chain fatty acids which can serve as ligands, stimulators for PPAR-α. In interstitial nephritis, PPAR-α was expressed in infiltrating eosinophils but not macrophages. In membranous nephropathy, nuclear staining for … More PPAR-α was more frequent than normal kidney.
2. Investigation on the expression of LBPs and PPARs in human cultured proximal renal tubular epithelial cells.
(1) Indirect immunofluorescence method and immunoblotting revealed that L-FABP and PPAR-α were expressed in human cultured proximal renal tubular epithelial cells. PAI-1 was also expressed in the cultured cells.
(2) PAI-1 antigen was detected in the medium of human cultured proximal renal tubular cells at a concentration of 250-600 ng/mL after the cells were cultured in the medium including several growth factors and bioactive molecules. Addition of hydrocortisone and epinephrine to the basic medium increased the concentration of PAI- 1 in the conditioned medium of the cultured cells. Hypoxia appeared to induce further the expression of PAI-1 in the cells cultured in the growth medium.
3. Analysis of relationships between clinical variables and advanced renal disease and vascular disease.
In hemodialysis patients with high HDL-C status, cholesteryl ester transfer protein (CETP) was a protective factor against vascular disease. A common C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was associated with increased serum levels of homocysteine which causes oxidative stress to endothelial cells. The homozygous mutants (TT genotype) were younger at the induction of hemodialysis and had a shorter duration of dialysis, suggesting that hyperhomocysteinemia may be related to accelerated progression of renal damage and mortality after initiation of dialysis. Among diabetic patients, PAI-1 concentrations in urine were higher in those with severe proteinuria over 1000 mg/gCr than those with microalbuminuria, while plasma PAI-1 levels were unchanged during progression of diabetic nephropathy. Urinary PAI-1 levels were positively associated with urinary NAG and sugar levels. Less

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Kimura H: "Cholesteryl ester transfer protein as a protective factor against vascular disease in hemodialysis patients"Am. J. Kidney Dis.. 38. 70-76 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H: "Effects of PAI-1 4G/5G genetic polymorphism on fibrinolytic system and nephropathy progression in NIDDM patients. Recent Advances in Diabetic Nephropathy"Proceedings of the 15 th Niigata Symposium of Nephrology Diabetic Nephropathy -from Bench to Bedside-. 15. 64-71 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto C: "Experimental glomerulonephritis induced by Haemophillus parainfluenzae in murine model"Nephron. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H: "AC677T mutation in the methylenetetrahydrofolate reductase gene modifies serum cysteine in dialysis patients"Am. J. Kidney Dis.. 36. 925-933 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H: "The methylguanidine to creatinine ratio, serum NOx concentrations and vascular disease in nondiabetic hemodialysis patients"Clin Exp Nephrol. 4. 231-235 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H: "The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients"J. Am. Soc. Nephrol.. 11. 885-893 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsukahara H: "Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease"Pediat. Int.. 42. 236-240 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H.: "The methylenetetrahydrofolate reductase gene mutation in hemodialysis patients"J. Am. Soc. Nephrol.. 11. 885-893 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H.: "The rhethylguanidine to creatinine ratio, serum Nox concentrations and vascular disease in nodiabetic hemodialvsis oatients"Clin Exp. Nephrpl. 4. 231-235 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H.: "A C677T mutation in the methylenetetrahydrofolatereductase gene modifies serum cysteine in dialysis patients"Am. J. Kidney Dis.. 36. 925-933 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsukahara H.: "Methylenetetrahydrofolate reductase polymorphismin Kawasaki disease"Pediat. Int.. 742. 236-240 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H.: "Cholesteryl ester transfer protein as a protective factoragainst vascular disease in hemodialysis patients."Am.J. KidneyDis. 38. 70-76 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H.: "Effects of PAI-1 4G/5G genetic polymorphism onfibrinolytic system and nephropathy progression in NIDDM patients"Recent Advances in Diabetic Nephropathy. Proceedings of the 15th Niigata symposium of Nehrology. Diabetic nephropathy-from Bench to Bedside. 15. 64-71 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okada T.: "The plasma levels of total PAI-1 and its relations with clinical variables in NIDDM patients."Jpn. 3. Clin. Lab. Autom.fo. 26. 33-39 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto C.: "Experimental glomerulonephritis induced byHeamophillus Influenzae in murine model"Nephron. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura H: "Cholesteryl ester transfer protein as a protective factor against vascular disease in hemodialysis patients"Am. J. Kidney Dis.. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura H: "Effects of PAI-1 4G/5G genetic polymorphism on fibrinolytic system and nephropathy progression in NIDDM patients. Recent Advances in Diabetic Nephropathy"Proceedings of the 15^<th> Niigata Symposium of Nephrology Diabetic Nephropathy -from Bench to Bedside-. 15. 64-71 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamot C: "Experimental glomerulonephritis induced by Haemophillus parainfluenzae in murine model"Nephron. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Kimura et al: "Effects of PAI-1 4G/5G genetic polymorphism on fibrinolytic system and nephropathy progression in NIDDM patients."Recent Advances in Diabetic Nephropathy. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Kimura et al: "A C677T mutation in the methylenetetrahydrofolate reductase gene modifies serum cysteine in dialysis patients."Am.J.Kidney Dis.. 36. 925-933 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Kimura et al: "The methylguanidine to creatinine ratio, serum NOx concentrations and vascular disease in nondiabetic hemodialysis patients."Clin Exp Nephrol. 4. 231-235 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Kimura et al: "The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients."J.Am.Soc.Nephrol.. 11. 885-893 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Tsukahara et al: "Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease."Pediat.Int.. 42. 236-240 (2000)

    • Related Report
      2000 Annual Research Report

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

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