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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   115 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

Authors

Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Yong Liu PhD Assistant 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
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d