Analysis of the inhibitory effects of peroxsome proliferator-activated receptors on glomerular injury

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• 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)
• 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
• 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

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.

Free Research Field

腎臓内科学