Involvement of antioxidant defense mechanisms in the pathogenesis of renal damage
| Project/Area Number |
23591585
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUSAKA Taiji 東海大学, 医学部, 准教授 (50317749)
MOCHIZUKI Hiroyuki 東海大学, 医学部, 教授 (50270856)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 腎障害 / 酸化ストレス / 抗酸化防御機構 / Keap1 / Nrf2 / シクロスポリン / 糸球体硬化 / 間質繊維化 |
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| Research Abstract |
Cyclosporine-induced nephrotoxicity was studied in Nrf2 knockout mice and Keap1 knockdown mice. The Keap1-Nrf2 system is known to play a central role in promoting antioxidant mechanisms. In Nrf2 knockout mice, in which the antioxidant Keap1-Nrf2 system is inactivated, cyclosporine A induces oxidative stress in the kidney and tubular damage, suggesting that Keap1-Nrf2 system plays a protective role in the pathogenesis of cyclosporine nephrotoxicity. However, in Keap1 knockdown mice, in which antioxidant mechanisms are constitutively activated, renal damage was not attenuated. These data suggest that, although antioxidant system is involved in attenuating cyclosporine nephrotoxicity, uncontrolled activation of Keap1-Nrf2 system is not always accompanied by beneficial effects in attenuating cyclosporine nephrotoxicity, suggesting that there may be some mechanisms other than oxidative stress in the pathogenesis of cyclosporine nephrotoxicity.
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Report
(4 results)
Research Products
(2 results)
