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Therapeutic strategies to tacrolimus-induced renal interstitial injury.

Research Project

Project/Area Number 16591613
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionOsaka City University

Principal Investigator

NAKATANI Tatsuya  Osaka City University, Med Sch, Dept Urol, Professor, 大学院・医学研究科, 教授 (40183511)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsrenal fibrosis / inflammation / NF-κB / curcumin / Rho-kinase / progressive renal disease / ureteral obstruction / 腎間質 / 線維化 / MCP-1 / 尿管結紮 / マクロファージ / タクロリムス
Research Abstract

Renal fibrosis, a main determinant for the prognosis of progressive renal disease, is usually preceded by interstitial inflammation. Therefore, it is hypothesized that prevention of inflammation is an important clue to retard the disease progression. Nuclear factor kappaB (NF-κB) is a ubiquitous transcription factor that plays a crucial role in inflammation. It has been recognized that continuous activation of NF-κB leads to the development of renal fibrosis. Several studies using Rho-kinase (ROCK) inhibitor, Y27632 or fasudil suggested the role of ROCK in tissue inflammation and fibrosis. In order to examine the interaction between NF-κB and ROCK, we examine the effects of fasudil on renal inflammation and fibrotic changes using rat model of chronic tacrolimus nephropathy and another renal fibrosis model induced by unilateral ureteral obstruction (UUO). Fasudil did not affect NF-κB activation, renal inflammation or fibrosis in tacrolimus nephropathy whereas it partially attenuated these changes in UUO rats. These results may indicate that relative role of ROCK differs with different etiology of renal fibrosis. It was also suggested that ROCK is involved, at least in part, in the activation of NF-κB observed in UUO rats. We also observed in UUO rats that a phenolic compound, curcumin partially attenuated NF-κB activation, renal inflammation or fibrosis but such effects were smaller than those observed using specific NF-κB inhibitor, pyrrolidine dithiocarbamate. It is important to search anti-inflammatory strategies via different route to prevent the progression of chronic renal disease.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004

All Journal Article (21 results)

  • [Journal Article] Molecular mechanisms and therapeutic strategies of chronic renal injury : The role of nuclear factor κB activation in the development of renal fibrosis.2006

    • Author(s)
      Tamada S, Asai T, Kuwabara N, Iwai T, Uchida J, Takemoto Y, Kaneda N, Yukimura T, Komiya T, Nakatani T, Miura K.
    • Journal Title

      Journal of Pharmacology Sciences. 100巻1号

      Pages: 17-21

    • NAID

      10018240945

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation. of renal fibrosis by curcumin in rat obstructive nephropathy.2006

    • Author(s)
      Kuwabara N, Tamada S, Iwai T, Teramoto K, Kaneda N, Yukimura T, Nakatani T, Miura K.
    • Journal Title

      Urology. 67巻2号

      Pages: 440-446

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Blood purification for critical illness : Cytokines adsorption therapy.2006

    • Author(s)
      Tsuchida K, Yoshimura R, Nakatani T, Takemoto Y.
    • Journal Title

      Therapeutic Apheresis and Dialysis. 10巻1号

      Pages: 25-31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular mechanisms and therapeutic strategies of chronic renal injury: The role of nuclear factor □B activation in the development of renal fibrosis.2006

    • Author(s)
      Tamada S, Asai T, Kuwabara N, Iwai T, Uchida J, Takemoto Y, Kaneda N, Yukimura T, Komiya T, Nakatani T, Miura K
    • Journal Title

      Journal of Pharmacology Sciences 100-1

      Pages: 17-21

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy.2006

    • Author(s)
      Kuwabara N, Tamada S, Iwai T, Teramoto K, Kaneda N, Yukimura T, Nakatani T, Miura K
    • Journal Title

      Urology 67-2

      Pages: 440-446

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Blood purification for critical illness : Cytokines adsorption therapy.2006

    • Author(s)
      Tsuchida K, Yoshimura R, Nakatani T, Takemoto Y
    • Journal Title

      Therapeutic Apheresis and Dialysis 10-1

      Pages: 25-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy.2006

    • Author(s)
      Kuwabara N, Tamada S, Iwai T, Teramoto K, Kaneda N, Yukimura T, Nakatani T, Miura K
    • Journal Title

      UROLOGY 67巻2号

      Pages: 440-446

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Molecular mechanisms and theraeutic strategies of chronic renal injury : The role of nuclear factor κB activation in the development of renal fibrosis.2006

    • Author(s)
      Tamada S, Asai T, Kuwabara N, Iwai T, Uchida J, Teramoto K, Kaneda N, Yukimura T, Komiya T, Nakatani T, Miura K
    • Journal Title

      J Pharmacol Sci 100巻

      Pages: 17-21

    • Related Report
      2005 Annual Research Report
  • [Journal Article] アンチセンス法を用いた腎虚血再灌流傷害軽減の展望2006

    • Author(s)
      吉村力勇, 松山昌秀, 仲谷達也
    • Journal Title

      炎症と免疫 14巻1号

      Pages: 95-103

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 分子標的治療:何をターゲットにすべきか2006

    • Author(s)
      木下義久, 鞍作克之, 仲谷達也
    • Journal Title

      Urology View 14巻1号

      Pages: 76-82

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Influence of glucose and inflammatory cytokines on TGF-β1 and CTGF mRNA expressions in human peritoneal mesothelial cells.2005

    • Author(s)
      Sakamoto N, Sugimura K, Kawashima H, Tsuchida K, Takemoto Y, Naganuma T, Nakatani T
    • Journal Title

      Int J Mol Med 15巻

      Pages: 907-911

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 腎移植における腎機能評価としての画像診断2005

    • Author(s)
      熊田憲彦, 仲谷達也
    • Journal Title

      Radiology Frontier 8巻1号

      Pages: 27-32

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Edaravone inhibits acute renal injury and cyst formation in cisplatin-treated rat kidney.2004

    • Author(s)
      Iguchi T, Nishikawa M, Chang B, Muroya O, Sato EF, Nakatani T, Inoue M.
    • Journal Title

      Free Radical Research. 38巻4号

      Pages: 333-341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Kidney transplants from living related donors having double inferior vena cava.2004

    • Author(s)
      Nakatani T, Kim T, Naganuma T, Uchida J, Takemoto Y, Sugimura K
    • Journal Title

      Urologia Internationalis. 72巻4号

      Pages: 358-360

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Edaravone inhibits acute renal injury and cyst formation in cisplatin-treated rat kidney.2004

    • Author(s)
      Iguchi T, Nishikawa M, Chang B, Muroya O, Sato EF, Nakatani T, Inoue M
    • Journal Title

      Free Radical Research 38-4

      Pages: 333-341

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Kidney transplants from living related donors having double inferior vena cava.2004

    • Author(s)
      Nakatani T, Kim T, Naganuma T, Uchida J, Takemoto Y, Sugimura K
    • Journal Title

      Urologia Internationalis 72-4

      Pages: 358-360

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biological reactions resulting from endotoxin adsorped on dialysis membrane : an in vitro study2004

    • Author(s)
      Tsuchida K, Nakatani T, Sugimura K, Yoshimura R, Takemoto Y
    • Journal Title

      ARTIFICIAL ORGANS 28巻1号

      Pages: 1134-1142

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activation of transcription factors AP-1 and NF-kappaB in chronic cyclosporin A nephrotoxicity : role in beneficial effects of magnesium supplementation.2004

    • Author(s)
      Asai T, Nakatani T, Tamada S, Kuwabara N, Yamanaka S, Tashiro K, Nakao T, Komiya T, Okamura M, Kim S, Iwao H, Miura K
    • Journal Title

      TRANSPLANTATION 75巻

      Pages: 1040-1044

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Biological reaction by mediating reaction of endotoxin adsorbed dialysis membrane.-In vitro study-2004

    • Author(s)
      Tsuchida K, Nakatani T, Sugimura K, Yoshimura R, Matsuyama M, Takemoto Y
    • Journal Title

      ARTIFICIAL ORGANS 28巻2号

      Pages: 231-234

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The expression of cyclooxygenases and lipoxygenases in renal ischemia-reperfusion injury.2004

    • Author(s)
      Matsuyama M, Nakatani T, Hase T, Kawahito Y, Sano H, Kawamura M, Yoshimura R
    • Journal Title

      Transplant Proc 36巻7号

      Pages: 1939-1942

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 多臓器不全への進展を防止する新しい治療戦略CTR2004

    • Author(s)
      武本佳昭, 土田健司, 吉村力勇, 仲谷達也
    • Journal Title

      日本アフェレシス学会雑誌 23巻1号

      Pages: 93-100

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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