Analysis of the inhibitory effects of peroxsome proliferator-activated receptors on glomerular injury
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 |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | University of Fukui |
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)
|
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)
|
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 |
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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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Short-chain fatty acids, GPR41 and GPR43 ligands, inhibit TNF-α-induced MCP-1 expression by modulating p38 and JNK signaling pathways in human renal cortical epithelial cells.2017
Author(s)
Kobayashi M, Mikami D, Kimura H, Kamiyama K, Morikawa Y, Yokoi S, Kasuno K, Takahashi N, Taniguchi T, Iwano M.
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Journal Title
Biochem Biophys Res Commun.
Volume: 486
Issue: 2
Pages: 499-505
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of novel variants in HLA class II region related to HLA DPB1 expression and disease progression in patients with chronic hepatitis C.2017
Author(s)
Hiramatsu K, Matsuda H, Nemoto T, Nosaka T, Saito Y, Naito T, Takahashi K,Ofuji K, Ohtani M, Suto H, Yasuda T, Hida Y, Kimura H, Soya Y, Nakamoto Y.
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Journal Title
J Med Virol.
Volume: in press
Issue: 9
Pages: 1574-1583
DOI
Related Report
Peer Reviewed / Open Access
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