| Project/Area Number |
15K09252
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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 | University of Fukui |
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Principal Investigator |
Kimura Hideki 福井大学, 学術研究院医学系部門(附属病院部), 准教授 (20283187)
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| Co-Investigator(Kenkyū-buntansha) |
岩野 正之 福井大学, 学術研究院医学系部門, 教授 (20275324)
菅谷 健 聖マリアンナ医科大学, 医学部, 客員教授 (40381561)
糟野 健司 福井大学, 学術研究院医学系部門, 准教授 (60455243)
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| Project Period (FY) |
2015-10-21 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | PPAR-a / 糸球体上皮細胞障害 / 尿細管上皮細胞障害 / PPAR-ｄ / PPAR欠損マウス / アポトーシス / PPAR-α / PPAR-δ / オートファジー / L-FABP / 糸球体硬化 / PPAR-d / mProx |
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| Outline of Final Research Achievements |
PPAR-a deficient (KO) mice as well as control mice (S129) were injected once with doxorubicin (10mg/kg) via the tail vein at day 0. At day 3, day 7, week 2 and week 4, urinary protein levels were significantly higher in the KO mice than control mice. Serum Cr levels were significantly higher in the KO mice at 4 week. Glomerulosclerosis was also severer in the KO mice than the control at day 9 and week 4.5. Moreover, urinary excretion levels of podocalyxin as a specific marker of podocytes were significantly higher in the KO mice at days 3 and 7. In an immortalized mouse podocyte cell line treated with doxorubicin for 24 hours, amounts of cleaved caspase 3 and the percentage of apoptotic cells markedly increased. A PPAR-a agonist (fenofibrate) reduced the increases by 35-40%. In a mouse proximal tubular cell line, a PPAR-d activator (GW0742) weakened cisplatin-induced apoptosis by about 20%.
These findings suggest that different types of PPARs may protect against kidney injury.
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