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Delayed ischemic preconditioning contributes to renal protection by upregulation of miR-21. Kidney Int 2012 Dec;82(11):1167-75

Date

07/13/2012

Pubmed ID

22785173

Pubmed Central ID

PMC3777822

DOI

10.1038/ki.2012.241

Scopus ID

2-s2.0-84869212341 (requires institutional sign-in at Scopus site)   148 Citations

Abstract

Delayed 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.

Author List

Xu X, Kriegel AJ, Liu Y, Usa K, Mladinov D, Liu H, Fang Y, Ding X, Liang M

Author

Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Animals
Apoptosis
Apoptosis Regulatory Proteins
Cells, Cultured
Gene Knockdown Techniques
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Ischemic Preconditioning
Mice
MicroRNAs
RNA-Binding Proteins
Reperfusion Injury
Up-Regulation