title: miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice.
abstract: 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.
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jia
authors.forename: Jie
authors.initials: J
authors.lastname: Teng
authors.forename: Jianzhou
authors.initials: J
authors.lastname: Zou
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Zeljko J
authors.initials: ZJ
authors.lastname: Bosnjak
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Ding
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D015427:Reperfusion Injury / Q000517:prevention & control*; D014978:Xenon / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D051017:Apoptosis Regulatory Proteins; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; D014978:Xenon; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse