title: Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway.
abstract: OBJECTIVE
  Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism.
  
  
  METHODS
  Experimental animal investigation.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20-25 g.
  
  
  METHODS
  We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed.
  
  
  RESULTS
  Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide-induced acute kidney injury.
  
  
  CONCLUSIONS
  Our findings demonstrated that xenon preconditioning protected against lipopolysaccharide-induced acute kidney injury via activation of miR-21 target signaling pathways.
authors.affiliation: 1Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China. 2Kidney and Dialysis Institute of Shanghai, Shanghai, China. 3Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China. 4Department of Physiology, Medical College of Wisconsin, Milwaukee, WI.
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: Xie
authors.initials: X
authors.lastname: Wu
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Ding
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000187:drug effects* / Q000502:physiology*; D018805:Sepsis / Q000150:complications; D015398:Signal Transduction / Q000187:drug effects*; D014978:Xenon / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D035683:MicroRNAs; D014978:Xenon; C531950:MIRN21 microRNA, mouse
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