• Xialian Xu, Alison J Kriegel, Yong Liu, Kristie Usa, Domagoj Mladinov, Hong Liu, Yi Fang, Xiaoqiang Ding, and Mingyu Liang.
• Division of Nephrology, Shanghai Medical College, Fudan University, Zhongshan Hospital, Shanghai, PR China.
• Kidney Int. 2012 Dec 1;82(11):1167-75.

AbstractDelayed ischemic preconditioning effectively protects kidneys from ischemia-reperfusion injury but the mechanism underlying renal protection remains poorly understood. Here we examined the in vivo role of microRNA miR-21 in the renal protection conferred by delayed ischemic preconditioning in mice. A 15-min renal ischemic preconditioning significantly increased the expression of miR-21 by 4 h and substantially attenuated ischemia-reperfusion injury induced 4 days later. A locked nucleic acid-modified anti-miR-21 given at the time of ischemic preconditioning knocked down miR-21 and significantly exacerbated subsequent ischemia-reperfusion injury in the mouse kidney. Knockdown of miR-21 resulted in significant upregulation of programmed cell death protein 4, a proapoptotic target gene of miR-21, and substantially increased tubular cell apoptosis. Hypoxia-inducible factor-1α in the kidney was activated after ischemic preconditioning and blockade of its activity with a decoy abolished the upregulation of miR-21 in cultured human renal epithelial cells treated with the inducer cobalt chloride. In the absence of ischemic preconditioning, knockdown of miR-21 alone did not significantly affect ischemia-reperfusion injury in the mouse kidney. Thus, upregulation of miR-21 contributes to the protective effect of delayed ischemic preconditioning against subsequent renal ischemia-reperfusion injury.

25 keywords...

hide…