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The study of Immunological and hunodynamic factors which modify the pathophysiology of IgA nephropathy-the study using high IgA prone in bred strain (HIGA) of mice-

Research Project

Project/Area Number 11671034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MUSO Eri  Kyoto University, Cardiovascular Medicine, Lecturer, 医学研究科, 講師 (10190852)

Co-Investigator(Kenkyū-buntansha) ONO Takahiko  Kyoto University, Cardiovascular Medicine, Assistant, 医学研究科, 助手 (60243028)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHIGA mouse / IL-12 / IgA / NO / iNOS / Th1 / Th2 / L-NAME / IgA Nephropathy / TGFβ / CD4 / ACE阻害剤 / 半月体形成 / マクロファージ
Research Abstract

l. Induction of active crescentic glomerular lesion in HIGA mice by IL-12 administration
Method : Administration of recombinant IL-12 (30Ong/mouse) for 7 days to 25 week old HIGA mice in which constant high Serum IgA and renal TGFβ expression have already been established. Balb/c mice were used as control.
Results : In rIL-12 administered HIGA mice, following findings were noted ;
1) Significantly high frequency of crescent formation and interstitial inflammatory cell infiltration including macrophage and CD4 cells, 2) Significant suppression of IgA and increase of IgG1/IgG2a ratio 3) Decrease of glomerular IgA deposition 4) Augmentation of renal TGFβ expression.
2.Involvement of NO and effect of L-NAME in the IL-12 induced active crescentic glomerulonephritis in HIGA mice.
Methods : in rIL 12 (100, 300ng/mouse) with or without L-NAME (10nM/day) were administered in 30 week old HIGA mice.
Result : In rIL-12 administered mice, signifgcantly high urinary NO excretion was noted with active cres … More centic renal lesion both of which were significantly suppressed in L-NAME co-administered mice. No marked change of serum IgA was noted, however, suppression of renal IgA deposition. which was observed in IL-12 administered mice, was not noted in L-NAME co-administered mice. These results suggest the mediation of NO expression in IL-12 induced active lesion in HIGA mice. The intervention of NO involvement might be the potent therapeutic approach for the active inflammatory renal damage in IgA nephropathy.
3. Induction of intraglomerular pressure overload and analysis of the effects of antihypertensive agent on the renal lesion.
Method : Heminephrectomy was performed in HIGA mice at 5 week old and followed until 40 weeks of age ACE inhibitors and hydralasine as control were administered for heminephrectomized HIGA mice.
Results : 1) In heminephrectomized mice, marked accumulation of extracellular matrix with expression of cytokines such as TGFβ, TNFα, and IL6 and apoptosis were noted. 2) In temocapril administered mice, significant mprovement of proteinuria and matrix accumulation accompanied TGFβ were noted. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Nogaki F, et al: "Interleukin 12 induces crescentic glimerular lesions in a high IgA atrain of ddY mice."Nephrology Dialysis Transplantation. 15. 1146-1154 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makino T, et al: "Inhibitory effects of rosmarinic acid on the proliferation of cultured murine mesangial cells."Nephrology Dialysis Transplantation. 15. 1140-1145 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suyama K, et al: "Significant suppressive effect of low dose temocapril (TEM), an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats."Nephron. 86. 491-498 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata T, et al: "High Frequency of surface IgA positive plasma cells in the intestinal lamina propria of HIGA mice, a murine model of IgA nephropathy with hyper-serum IgA."Journal of Immunology. 165. 1387-1394 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oyama A, et al: "Up-regulated、TGF、β mRNA expression in splenic T cells of high IgA-prone (HIGA) mice, a murine model of IgA nephropathy with glomerulosclerosis"Nephron. (in print).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 武曾惠理: "IgA腎症の病態モデルと病変修飾の試み"メディカルビューポイント21. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nogaki F, et al.: "Interleukin 12 induces crescentic glimerular lesions in a high IgA atrain of ddY mice."Nephrology Dialysis Transplantation. 15. 1146-1154 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makino T, et al: "Inhibitory effects of rosmarinic acid on the proliferation of cultured murine mesangial cells."Nephrology Dialysis Transplantation. 15. 1140-1145 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suyama K, et al: "Sigificant suppressive effect of low dose temocapril (TEM), an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats."Nephron. 86. 491-498 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamata T, et al: "High Frequency of surface IgA positive plasma cells in the intestinal lamina propria of HIGA mice, a murine model of IgA nephropathy with hyper-serum IgA."Journal of Immunology. 165. 1387-1394 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oyama A, et al: "Up-regulated TGF-βmRNA expression in splenic T cells of high IgA-prone (HIGA) mice, a murine model of IgA nephropathy with glomerulosclerosis"Nephron. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nogaki F, et al: "Interleukin 12 induces crescentic glimerular lesions in a high IgA atrain of ddY mice."Nephrology Dialysis Transplantation. 15. 1146-1154 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Makino T, et al: "Inhibitory effects of rosmarinic acid on the proliferation of cultured murine mesangial-cells."Nephrology Dialysis Transplantation. 15. 1140-1145 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suyama K, et al: "Significant suppressive effect of low dose temocapril(TEM), an ACE inhibitor with biliary excretion.on FGS lesions in hypertensiye rats."Nephron. 86. 491-498 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kamata T, et al: "High Frequency of surface IgA positive plasma cells in the intestinal lamina propria of HIGA mice, a murine model of IgA nephropathy with hyper-serum IgA."Journal of Immunology. 165. 1387-1394 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oyama A, et al: "Up-regulated・TGF・β mRNA expression in splenic T cells of high IgA-prone(HIGA)mice, a murine model of IgA nephropathy with glomerulosclerosis"Nephron. (in print).

    • Related Report
      2000 Annual Research Report
  • [Publications] 武曾惠理: "IgA腎症の病態モデルと病変修飾の試み"メディカルビューポイント21. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] 武曾 惠理、他: "特集"IgA腎症30年",動物実験による新しい知見・展望"腎と透析. 46. 107-112 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawamura T et al.: "Ultrastructural localization of dominantly increased fibronectin in markedly thickened glomerular basement membrane in selectively mated murine high IgA strain(HIGA mice)"Nephron. 83. 146-153 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suyama K et al.: "Significant suppressive effect of low dose temocapril(TEM),an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats"Nephron. (in print). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nogaki F et al.: "Interleukin 12 induces crescentic glomerular leseions in a high IgA strain of ddY mice"Nephrology Dialysis Transplantation. (in print). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Muso E et al.: "The effect of Th1/Th2 dominance on the clinicopathological feature of human and murine model of IgA nephropathy"Proceeding of 4eme Symposium Franco-Japonais de Nephrologie conference. 1. 21-25 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 武曾 惠理: "IgA腎症とサイトカイン"医学のあゆみ. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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