| Project/Area Number |
13671104
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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 |
Kidney internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
UENO Mitsuhiro NIIGATA UNIVERSITY, Medical and dental hospital, Lecturer, 医歯学総合病院, 講師 (90260546)
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| Co-Investigator(Kenkyū-buntansha) |
GEJYO Fumitake NIIGATA UNIVERSITY, Medical and dental hospital, Professor, 医歯学総合病院, 教授 (20126410)
SAKATSUME Minoru NIIGATA UNIVERSITY, Medical and dental hospital, Assistant, 医歯学総合病院, 助手 (70334662)
NARITA Ichiei NIIGATA UNIVERSITY, Graduate school of medical and dental sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20272817)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | refractory glomerulonephritis / IgA nephropathy / crescentic glomerulonephritis / single nucleotide polymorphism / DNA microarray / macrophage metalloelastase / aldosterone Synthase / α addducin / 高血圧 / Macrophage mettalloelastase / α-adducin / アンジオテンシノーゲン / CYP11B2 / FcR受容体 / 多価免疫受容体 / ウテログロビン / DNAマイクロアレイ解析 / クラスタリング / 腎生検 / ネフローゼ症候群 |
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| Research Abstract |
Both IgA nephropathy and crescentic glomerulonephritis are typical of refractory glomerulonephritis. The precise onset mechanisms of both glomerulonephtitis are unknown. However genetical factors may be associated with the onset of IgA nephropathy because of familial clustering. We attempted to investigate the possible role of various gene polymorphisms in IgA nephropathy and studied any possible associations between gene variation and the clinical manifestations, especially renal prognosis in about 250 patients. As a result, we demonstrated that single nucleotide polymorphisms of polymeric immunoglobulin receptor, uteroglobin, angiotensin converting enzyme angiotensinogen aldosterone synthase, SA, α addducin and peroxisome proliferator-activated receptor γ were related to renal prognosis of IgA nephropathy.
Rat anti-glomerular basement membrane(GBM) nephritis is a model of crescentic glomerulonepnntis induced by the administration of anti-GBM antiserum. To elucidate the mechanism of gl
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omerular injury, we analyzed the gene expression patterns in the kidneys of anti-GBM nephritis rats using DNA arrays, and found that macropgage metalloelastase/matrix metalloproteinase(MMP)-12 was lone of the highly expressed genes in the kidneys on days 3 and 7 after the injection of anti-GBM antiserum. Enhancement of MMP-12 mRNA expression was confirmed by Northern blot analysis, and in situ hybridization revealed that MMP-12 mRNA was expressed in ED-1-positive macrophages and multinuclear giant cells in the glomeruli with crescent. Moreover, these cells were positive with anti-rat rMMP-12 Ab on the section of the kidneys of anti-GBM nephritis rats on day 7. To clarify the role of MMP-12, we conducted a neutralization experiment using anti-rat rMMP-12 Ab. Consequently, crescent formation and macrophage infiltration in the glomeruli were significantly rethiced in the rats treated with anti-rat rMMP-12 Ab, and the amount of urine protein was also decreased. These results disclosed that MMP-12 played an important role in glomerular injury in a crescentic glomerulonephritis model. Less
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