miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice. Anesthesiology 2013 Sep;119(3):621-30
Date
05/18/2013Pubmed ID
23681145Pubmed Central ID
PMC4428598DOI
10.1097/ALN.0b013e318298e5f1Scopus ID
2-s2.0-84883244264 (requires institutional sign-in at Scopus site) 59 CitationsAbstract
BACKGROUND: MicroRNAs participate in the regulation of numerous physiological and disease processes. The in vivo role of microRNAs in anesthetics-conferred organoprotection is unknown.
METHODS: Mice were exposed for 2 h to either 70% xenon, or 70% nitrogen, 24 h before the induction of renal ischemia-reperfusion injury. The role of microRNA, miR-21, in renal protection conferred by the delayed xenon preconditioning was examined using in vivo knockdown of miR-21 and analysis of miR-21 target pathways.
RESULTS: Xenon preconditioning provided morphologic and functional protection against renal ischemia-reperfusion injury (n = 6), characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress. Xenon preconditioning significantly increased the expression of miR-21 in the mouse kidney. A locked nucleic acid-modified anti-miR-21, given before xenon preconditioning, knocked down miR-21 effectively, and exacerbated subsequent renal ischemia-reperfusion injury. Mice treated with anti-miR-21 and ischemia-reperfusion injury showed significantly higher serum creatinine than antiscrambled oligonucleotides-treated mice, 24 h after ischemia-reperfusion (1.37 ± 0.28 vs. 0.81 ± 0.14 mg/dl; n = 5; P < 0.05). Knockdown of miR-21 induced significant up-regulation of programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10, two proapoptotic target effectors of miR-21, and resulted in significant down-regulation of phosphorylated protein kinase B and increased tubular cell apoptosis. In addition, xenon preconditioning up-regulated hypoxia-inducible factor-1α and its downstream effector vascular endothelial growth factor in a time-dependent manner. Knockdown of miR-21 resulted in a significant decrease of hypoxia-inducible factor-1α.
CONCLUSIONS: These results indicate that miR-21 contributes to the renoprotective effect of xenon preconditioning.
Author List
Jia P, Teng J, Zou J, Fang Y, Zhang X, Bosnjak ZJ, Liang M, Ding XMESH terms used to index this publication - Major topics in bold
Anesthetics, InhalationAnimals
Apoptosis Regulatory Proteins
Hypoxia-Inducible Factor 1, alpha Subunit
Ischemic Preconditioning
Kidney
Male
Mice
Mice, Inbred C57BL
MicroRNAs
PTEN Phosphohydrolase
RNA-Binding Proteins
Reperfusion Injury
Xenon
