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Molecular biological approach to the abnormalities of extracelluar matrix of the diabetic nephropathy.

Research Project

Project/Area Number 04671481
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionOkayama University

Principal Investigator

MAKINO Hirofumi  Okayama University Medical School, assistant, 医学部, 助手 (50165685)

Co-Investigator(Kenkyū-buntansha) SHIKATA Kenichi  Okayama University Medical School, assistant, 医学部, 助手 (00243452)
KASHIHARA Naoki  Okayama University Hospital, assistant, 医学部附属病院, 助手 (10233701)
IKEDA Shyuji  Okayama University Hospital, assistant, 医学部附属病院, 助手 (10212771)
NIMOMIYA Yoshifumi  Okayama University Medical School, professor, 医学部, 教授 (70126241)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsdiabetes mellitus / extracellular matrix / kidney / glomerulus / type IV collagen / gene / proteoglycans / immunoelectron microscopy / 成長因子 / 形質交換 / 系球体
Research Abstract

Extracellular matrix has been shown to be consisted of collagens, laminins and proteoglycans. In diabetic nephropathy, the altertions of biochemical properties of type IV collagen and the decreased expression of proteoglycans are considered to be major pathological changes of the disease and related to the phenotypic changes of glomerular cells. Immunoelectron microscopic studies of diabetic nepropathy patients with nephrotic syndrome showed the thicking of glomerular basement membranes (GBM), increased amount of type IV collagens with decreased density, and decreased heparan sulfate proteoglycan. These alterations of extracellular matrix components seems to contribute to the the impairment of size and charge barrier of the GBM and proteinuria. Furthermore, we cloned a novel chain of type IV collagen, i.e.alpha4 chain, which cDNA (NK4) included NC-1 domain and expands 1.9 Kb. Northern blot analyzes showed -9.5 Kb transcript. Immunofluorescence studies of alpha1, alpha2, alpha3, alpha4, and basement membrane associated-collagen (BAC) showed alpha1 and alpha2 localized to the glomerular mesangial area and glomerular capillary, while alpha3 and alpha4 localized mainly along the capillary wall. BAC immunoreactivity was observed in the mesangial area. In the kidney of diabetic patients, expanded mesangial matrix and thickened GBM showed increased expression of alpha1-alpha4 chains and BAC.Furthermore, we analyzed the expression of the interstitial collagens, such as III,V,VI collagens. Type III collagen exclusively expressed in the interstinum of the kidney and type V and VI collagens had mesangial expressions. In diabetic kidney, these collagens were increased in the mesangial area.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Makino H et al.: "Ultrastructunl changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy." Laboratory Investigation. 68. 45-55 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hironaka K et al.: "Renal basement membranes by ultrahigh resulution scanning elecron micruscopy." Kidney International. 43. 334-345 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H et al.: "Localization of fibril/microfibril and basement membrance collagen in diabetic glomerulosclerosis in type 2 dinbetos." Diabeti Medicine. 11. 304-311 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H et al.: "Immunoreactivity of the JK-132monoclonal antibody directed agninst basement membranecollagen in normal and diabetic glomeruli." Virclows Ardir. 424. 235-241 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Morioka S: "Chnges in plasma concentrations of vitronectin in patients with diabetic nephropathy" Acta Media Okayama. 48. 137-142 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H.: "Molecular biology of regulators of extrucellular matrix in glomerular injyurios." Connective Tissue. 25. 201-216 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H et al.: "GBrowth factors and diabetic nephropathy" Igaku no Ayumi. 171. 575-579 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H.: "Molecular biology of glomerular hypertrophy and sclocrusis.-Mesnngial cells-" Kidney and Dialysis. 37. 679-684 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H., et al.: "Ultrastructual changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy." Laboratory Investigation. 68. 45-55 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hironaka K., et al.: "Renal basement membranes by ultrahigh resolution scanning electron microscopy" Kidney International. 43. 334-345 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H., et al.: "Localization of fibril/microfibril and basement membrane collagen in diabetic glomerulosclerosis in type 2 diabetes." Diabetic Medicine. 11. 304-311 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H., et al.: "Immunoreactivity of the JK-132 monoclonal antibody directed against basement membrane collagen in normal and diabetic glomeruli." Virchows Archiv. 424. 235-241 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Morioka S., et al.: "Changes in plasma concentrations of vitronectin in patients with diabetic nephropathy" Acta Med Okayama. 48. 137-142 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H: "Molecular biology of regulators of extracellular matrix in glomerular injyuries." Connective Tissue. 25. 201-2-6 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H., et al.: "Growth factors and diabetic nephropathy." Igaku no Ayumi. 171. 575-579 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makino H.: "Molecular biology of glomerular hypertrophy and scloerosis. -Mesangial cells-" Kidney and Dialysis. 37. 679-684 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Makino,et al: "Localization of Fibril/Microfibril and Basement Membrane Collagens in Diabetic Glomerulosclerosis in Type2 Diabetes" Diabetic Medicine. 11. 304-311 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Makino,et al: "Immunoreactivity of the JK-132 Monoclonal Antibody Directed against Basement Membrane Collagen in Normal and Diabetic Glomerali" Virchows Archiv. 424. 235-241 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 槇野博史: "分子レベルでみた糸球体の肥大と硬化-メサンギウム細胞" 腎と透析. 37. 679-684 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 槇野博史・杉本光: "成長因子と糖尿病性腎症" 医学のあゆみ. 171. 575-579 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Haramoto T,Makino H,Ikeda S,Ota Z: "Vltrastructural localization of three basement membrane components,-Type IV collagen,heparan sulfate proteoglycan and laminin in the normal human GBM." Jpn J Nephrol. 35. 933-939 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 林義和,槙野博史 他: "糖尿病患者における血中,尿中メタロプロテアーゼインヒビター(TIMP)濃度" 日本糖尿病学会誌. 36. 661-663 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ota K,Ota Z,Shikata K,Makino H: "Ultrastructural changes of the glomerular basement membrane in diabetic nephropathy revealed by newly divised tissue negative statning method." Acta Med Okayama. 47. 267-272 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirofumi Makino: "Extracellular matrix in glomerular disease.In:Molecular and biological approach to glomerular injuries" Nishimura Smith-Gordon, 12 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 槙野博史,柏原直樹,渡辺有三,太田善介: "糖尿病性慢性合併症発症機序へのアプローチ プロテオグリカン代謝異常の立場から 糖尿病学の進歩'93 第27集" 診断と治療社, 4 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirofumi Makino: "Ultrastructural changes of extracellular matrices in diabetic nephropathy revealed by high resolution scannirg and immunoelectron microscopy" Laboratory Investigation. 68. 45-55 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hirofumi Makino: "Distribution of a novel chain of basement membrane associated collagen in the renal tissue" Connective Tissue. 24. 163-168 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 槙野 博史: "糸球体硬化における細胞外基質の分子生物学的研究" 日本臨床. 50. 3038-3045 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 槙野 博史: "糖尿病における腎・糸球体肥大と硬化のメカニズム" 腎と透析. 33. 855-860 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 槙野 博史: "糖尿病性腎症におけるコラーゲンの異常-特にIV型コラーゲン鎖について -糖尿病記録書1992" 医学図書出版株式会社, 4(221-224) (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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