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Protective Role of the Natriuretic Peptide System in Tissue Injury and Remodeling

Research Project

Project/Area Number 13671152
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MUKOYAMA Masashi  Kyoto University Graduate School of Med., Lecturer, 医学研究科, 講師 (40270558)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsNatriuretic peptide / Transgenic mouse / Glomerulonephritis / Diabetic nephropathy / Renal fibrosis / Mesangial cell / Endothelial protection / Vascular regeneration / 腎間質線維化 / 細胞外基質 / 腎保護
Research Abstract

In prder to explore the rote of natriuretic peptides, with potent diuretic and vasorelaxing properties, in tissue injury and remodeling, we investigated the effect of chronic excess of brain natriuretic peptide (BNP) in transgenic mice on renal injuries using various nephropathy models
In a model of anti-glomerular-basement-membrane antibody glomerulonephritis (GN), control nontransgenic mice developed progressive GN with heavy prateinuria (21 times of baseline level) and severe glomerular/tubulointerstitial damage at 8-12 weeks. In contrast, BNP-transgenic mice (BNP-Tg) showed only minor and transient proteinuria with no apparent tissue damage. Gene expression of transforming growth factorβ (TGF-β) and monocyte chemoattractant protein-1 (MCP-1) as well as the activation of ERK/MAP kinase within renal tissues was much reduced in BNP-Tg, suggesting that these worked together to ameliorate renal injuries
In a model of renal fibrosis with unilateral ureteral obstruction (UUO), interstitial … More fibrosis was significantly ameliorated in BNP-Tg as compared with control nontransgenic mice. TGF-β expresstan was much reduced in BNP-Tg. Subsequent analysis revealed that the blood fbw in the renal peritubular capillary was significantly maintained in BNP-Tg, suggesting that such mechanisms of vascular protection may act against the progression of fibrotic processes
In a model of diabetic nephropathy, control mice developed significant proteinuria with masangial expansion 16 weeks after the onset of streptozotocin-induced diabetes. These changes were significantly milder in BNP-Tg. BNP inhibited the mesangial up regulation of TGF-β in vivo and in vitro, suggesting that this may provide a common key mechanism of renoprotection
These results indicate that natriuretic peptides potentially exert renoprotective effects by counteracting the fibrogenic stimuli such as TGF-βand MCP-1, suggesting that the activation of the natriuretic peptide system should be clinically applicable against various nephropathies Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Takayoshi Suganami: "Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury"Journal of the American Society of Nephrology. 12(12). 2652-2663 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masayo Nakagawa: "Monoclonal antibody against brain natriuretic peptide and characterization of brain-natriuretic peptide-transgenic mice"Journal of Hypertension. 19(3). 475-483 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideki Yokoi: "Role of connective tissue growth factor in profibrotic action of transforming growth factor-β : A potential target for preventing renal fibrosis"American Journal of Kidney Diseases. 38(4). S134-S138 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideki Yokoi: "Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis"American Journal of Physiology Renal Physiology. 282(5). F933-F942 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akihiro Yoshimoto: "Plasma ghrelin and desacyl glirelin concentrations in renal failure"Journal of the American Society of Nephrology. 13(11). 2748-2752 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masahisa Goto: "Expression and role of angiotensin II type 2 receptor in the kidney and mesangial cells of spontaneously hypertensive rats"Hypertension Research. 25(1). 125-133 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hisashi Makino: "Prevention of diabetic nephropathy in rats by prostaglandin E receptor EP1-selective antagonist"Journal of the American Society of Nephrology. 13(7). 1757-1765 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hisashi Makino: "Roles of connective tissue growth factor and prostanoids in early streptozotocin-induced diabetic rat kidney : The effect of aspirin treatment"Clinical and Experimental Nephrology. 7(1). 33-40 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazutomo Sawai: "Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis"Journal of the American Society of Nephrology. 14(5). 1154-1163 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takayoshi Suganami, et al.: "Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury"Journal of the American Society of Nephrology. 12 (12). 2652-2663 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masayo Nakagawa, et al.: "Monoclonal antibody against brain natriuretic peptide and characterization of brain natriuretic peptide-transgenic mice"Journal of Hypertension. 19 (3). 475-483 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideki Yokoi, et al.: "Role of connective tissue growth factor in profibrotic action of transforming growth factor-β: A potential target for preventing renal fibrosis"American Journal of Kidney Diseases. 38 (4). S134-S138 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideki Yokoi, et al.: "Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis"American Journal of Physiology. 282 (5). F933-F942 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akihiro Yoshimoto, et al.: "Plasma ghrelin and desacyl ghrelin concentrations in renal failure"Journal of die American Society of Nephrology. 13 (11). 2748-2752 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masahisa Goto, et al.: "Expression and role of angiotensin II type 2 receptor in the kidney and mesangial cells of spontaneously hypertensive rats"Hypertension Research. 25(1). 125-133 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hisashi Makino, et al.: "Prevention of diabetic nephropathy in rats by prostaglandin E receptor EPl-selective antagonist"Journal of the American Society of Nephrology. 13 (7). 1757-1765 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hisashi Makino, et al.: "Roles of connective tissue growth factor and prostanoids in early streptozotocin-induced diabetic rat kidney: The effect of aspirin treatment"Clinical and Experimental Nephrology. 7(1). 33-40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazutomo Sawai, et al.: "Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis"Journal of the American Society of Nephrology. 14 (5). 1154-1163 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazutomo Sawai: "Angiogemc protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis"Journal of the American Society of Nephrology. 14(発表予定). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hisashi Makino: "Roles of connective tissue growth factor and prostanoids in early streptozotocin-induced diabetic rat kidney : The effect of aspirin treatment"Clinical and Experimental Nephrology. 7(発表予定). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hisashi Makino: "Prevention of diabetic nephropathy in rats by prostaglandin E receptor EP_1-selective antagonist"Journal of the American Society of Nephrology. 13(7). 1757-1765 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hideki Yokoi: "Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis"American Journal of Physiology Renal Physiology. 282(5). F933-F942 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akihiro Yoshimoto: "Plasma ghrelin and desacyl ghrelin concentrations in renal failure"Journal of the American Society of Nephrology. 13(11). 2748-2752 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masahisa Goto: "Expression and role of angiotensin II type 2 receptor in the kidney an mesangial cells of spontaneously hypertensive rats"Hypertension Research. 25(1). 125-133 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayoshi Suganami: "Overexpression of brain natriuretic peptide in mice ameliorates immune-mediated renal injury"Journal of the American Society of Nephrology. 12・12. 2652-2663 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masayo Nakagawa: "Monoclonal antibody against brain natriuretic peptide(BNP)and characterization of BNP-transgenic mice"Journal of Hypertension. 19・3. 475-483 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hideki Yokoi: "Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis"American Journal of Physiology. 282(発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masahisa Goto: "Expression and role of angiotensin II type 2 receptor in the kidney and mesangial cells of spontaneously hypertgpsive rats"Hypertension Research. 25・1. 125-133 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hideki Yokoi: "Role of connective tissue growth factor in profibrotic action of transforming growth factor-β: A potential target for preventing renal fibrosis"American Journal of Kidney Diseases. 38・4(Suppl1). S134-S138 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takayoshi Suganami: "Altered growth response to prostaglandin E_2 and its receptor signaling in mesangial cells from stroke-pronespontaneously hypertensive rats"Journal of Hypertension. 19・6. 1095-1103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masashi Mukoyama: "Role of adrenomedullin and its receptor system in renal pathophysiology"Peptides. 22・11. 1925-1931 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takatoshi Saito: "Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells"American Journal of Physiology. 281・3. H1364-H1371 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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