role of p21 activation and senescence on acute kidney injury

Research Project

Project/Area Number	25860190
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	General pharmacology
Research Institution	Kagawa University
Principal Investigator	NAKANO Daisuke 香川大学, 医学部, 助教 (30524178)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords	急性腎障害 / 細胞周期 / p21 / プレコンディショニング / 再生
Outline of Final Research Achievements	We investigated the role of p21 in acute kidney injury and ischemic preconditioning (IPC). Mice lacking p21 (p21-KO) and wild-type mice underwent renal ischemia followed by reperfusion (I/R). I/R increased p21 expression in the kidneys. The acute kidney injury was worse in p21-KO mice than in wild-type mice. The results suggest that p21 confers tolerance to I/R injury. IPC attenuated I/R injury in wild-type mice, but not in p21-KO mice. IPC decreased the number of proliferating tubular cells before I/R and increased it at 24 h after I/R in the kidney of wild-type mice. In p21-KO mice, IPC did not change the number of proliferating cells before I/R, and decreased it after I/R. IPC increased renal p21 expression and the number of cells in the G1 phase of the cell cycle before I/R. In conclusion, renal p21 is essential for the beneficial effects of renal IPC.