| Project/Area Number |
24591217
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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 |
Kidney internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
SHIMIZU Akira 日本医科大学, 医学(系)研究科(研究院), 教授 (00256942)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASAKA Shinya 日本医科大学, 医学部, 助教 (00573239)
MASUDA Yukinari 日本医科大学, 医学部, 講師 (70173755)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ANCA / ANCA関連腎炎 / ANCA関連血管炎 / 抗好中球細胞質抗体 / 半月体形成性糸球体腎炎 / 抗糸球体基底膜抗体腎炎 / サイトカイン / NETs / 壊死性半月体形成性腎炎 / 抗糸球体基底膜抗体病 / 壊死性糸球体腎炎 / 糸球体腎炎 |
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| Outline of Final Research Achievements |
In ANCA-associated vasculitis (AAV), necrotizing and crescentic glomerulonephritis (NCGN) was induced in WKY rats by immunization with human MPO (hMPO). The induced anti-hMPO Antibody (Ab) cross-reacted with rat neutrophils with activation in vitro. The crescent formation with NETs in glomeuli was enhanced by the additional injection of sub-nephritogenic anti-GBM Ab, whereas it was not significantly enhanced by the additional administration of TNF-α or G-CSF in vivo. NCGN rats with the sub-nephritogenic anti-GBM Ab showed elevated albuminuria and serum TNF-α, CXCL1 and CXCL2 levels. TNF-α, CXCL1, CXCL2 and CXCL8, which are mainly involved in neutrophil-endothelial interactions, were increased in glomeruli. Our results demonstrated that the acceleration of NCGN in AAV may be necessary not only accumulation of neutrophils in glomeruli, but also aberrant activation of neutrophils with increased glomerular expression of neutrophil activation-associated cytokines and chemokines.
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