| Project/Area Number |
25461238
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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 | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KASHIHARA Naoki 川崎医科大学, 医学部, 教授 (10233701)
SATOH Minoru 川崎医科大学, 医学部, 准教授 (70449891)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 尿細管間質障害 / エストロゲン / ラロキシフェン / 蛋白尿 / ミトコンドリア / 酸化ストレス / 尿細管障害 / インフラマソーム / エストロゲン受容体刺激 / 脂肪酸結合アルブミン / 慢性腎臓病 / Raloxifene / 選択的エストロゲン受容体刺激薬 / アポトース |
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| Outline of Final Research Achievements |
Ｗe investigated whether the selective estrogen receptor modulator, raloxifene, could attenuate albumin-induced tubular injury through reducing mitochondrial oxidative stress.ICR-derived glomerulonephritis (ICGN) mice, a mouse strain with a hereditary nephrotic syndrome, underwent ovariectomy, and were treated with raloxifene (50μg/kg/day) for 6 weeks. Ovariectomy induced the apoptotic cell death in renal proximal cells (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining) and decreased cytochrome-c oxidase activity in mitochondria. Electron microscopy of the ovariectomized ICGN mice revealed morphologically abnormal mitochondria, and these changes were suppressed following treatment with raloxifene with upregulation of the mitochondrial thioredoxin system. Stimulation of estrogen receptor attenuated programmed cell death in renal proximal tubules induced by albumin-overload as a result of amelioration of mitochondrial dysfunction.
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