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Molecular analysis of type IV collagen accumulation in diabetic nephropathy

Research Project

Project/Area Number 05670853
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionShiga University of Medical Science

Principal Investigator

KIKKAWA Ryuichi  Shiga University of Medical Science, Third Department of Medicine, Associate Professor, 医学部, 助教授 (50093406)

Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsDiabetic nephropathy / Type IV collagen / PKC / MAP kinase / vasoactive substance / mRNA / 血管作働性物質 / 分子生物学 / メサンギウム細胞 / グルコース
Research Abstract

The mesangial expansion in glomerulis considered to be a cardinal lesion of diabetic nephropathy. The lesion is caused by the accumulation of various matrix proteins, especially of type IV collagen. So, it is important to know how type IV collagen accumulate in mesangial area in order to clarify the pathogenesis of diabetic nephropathy.
We have previous published that high concentration of glucose increases type IV collagen production in glomerular mesangial cells via its metabolic effect. In an attempt to investigate the mehanism why glucose increases type IV collagen production, the linkage between type IV collagen production and metabolic consequences to high concentration of glucose was analyzed in rat cultured mesangial cells. High concentration of glucose caused significant activation of protein kinase C (PKC) as well as of mitogen-associated protein (MAP) kinase. Various vasoactive substances, which are able to activate PKC and MAP kinase, are observed to stimulate type IV collagen production. However, any change in mRNA level for type IV collagen was not detected by northern blotting using VI (alpha_1) cDNA in mesangial cells cultured under high glucose condition. mRNAs for MMP-2 and -9, which were responsible for degrading type IV cllagen were neither changed in those experiments.
It is concluded from these results that glucose may activate PKC and MAP kinase, and may in turn stimulate type IV collagen production, which might be associated with the accumulation of type IV collagen in diabetic glomeruli.

Report

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

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 宇津 貴、吉川隆一: "高糖濃度条件下培養メサンギウム細胞におけるプロテインキナーゼCの変化" 糖尿病. 36. 343-348 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kikkawa R, Haneda M,: "Translocation of protein kinase C α ζ and in rat mesangial cells cultured high under glucose conditions." Diabetologia. 37. 838-841 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 杉本俊郎、吉川隆一、: "培養ラットメサンギウム細胞のMAPキナーゼ活性" 糖尿病記録号1993. 270-272 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sugimoto T, Kikkawa R,: "Atrial natriuretic peptide inhibits endothelin- I - induced activation of mitogen-activated protein kinase in cultured rat mesangial cells." Biochem Bjophys Res Commun. 195. 72-78 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Haneda M, Kikkawa R,: "Abnormalities in protein C and MAP kinase cascade in mesangilal cells cultured under high glucose conditions." 4 th International Symposium on Hypertension Associated with Diabetes Mellitus, Otsu, 1994.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 澤田正史、吉川隆一、: "ラット培養メサンギウム細胞における4型コラーゲン産生能に及ぼす細胞増殖因子および血管作働物質の影響" 第36回日本腎臓学会総会、1993.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kikkawa R,Haneda M,et al: "Atrial natriuretic peptide inhibits endothelin-I-induced activation of mitogen-activated protein kinase in cultured rat mesangial cells." Diabetologia. 37. 838-841 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sugimoto T,Kikkawa R,et al: "Atrial natriuretic peptide inhibits endothelin-I-induced activation of mitogen-activated protein kinase in" Biochem Biophys Res Commun. 195. 72-78 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Haneda M,Kikkawa R,et al: "Abnormalities in protein kinase C and MAP kinase cascade in mesangial cells cultured under high glucose conditions." 4th International Symposium on Hypertension Associated with Diabetes Mellitus, Otsu. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 澤田正史: "ラット培養メサンギウム細胞におけるIV型コラーゲン産生能に及ぼす細胞増殖因子および血管作働性物質の影響" 第36回日本腎臓学会総会抄録集. 308 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sawada T: "Amelioration by aldose reductase inhibitors of type IV collagen production in cultured rat mesangial cells under high glucose condition" US-Japan aldose reductase workshop. 4 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 羽田勝計: "糖尿病学の進歩 第27巻" 日本糖尿病学会編,診断と治療社, 243 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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