Therapeutic strategies to tacrolimus-induced renal interstitial injury.
| Project/Area Number |
16591613
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Osaka City University |
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Principal Investigator |
NAKATANI Tatsuya Osaka City University, Med Sch, Dept Urol, Professor, 大学院・医学研究科, 教授 (40183511)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | renal 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 |
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| 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.
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Report
(3 results)
Research Products
(21 results)
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[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.
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Journal Title
Journal of Pharmacology Sciences. 100巻1号
Pages: 17-21
NAID
Description
「研究成果報告書概要(和文)」より
Related Report
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[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
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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
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[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
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Journal Title
J Pharmacol Sci 100巻
Pages: 17-21
Related Report
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[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
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Journal Title
TRANSPLANTATION 75巻
Pages: 1040-1044
Related Report
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