title: microRNA-183 Mediates Protective Postconditioning of the Liver by Repressing Apaf-1.
abstract: Ischemic postconditioning (iPoC) is known to mitigate ischemia-reperfusion (IR) injury of the liver, the mechanisms of which remain to be elucidated. This study explored the role of microRNA-183 (miR-183) in the protective mechanism of iPoC.
  
  
  
  Microarray analysis showed miR-183 was robustly expressed in rats' livers with iPoC. miR-183 repressed the mRNA expression of Apaf-1, which is an apoptosis promoting factor. Using an oxygen-glucose deprivation (OGD) injury model in Clone 9 cells, hypoxic postconditioning (HPoC) and an miR-183 mimetic significantly decreased cell death after OGD, but miR-183 inhibitors eliminated the protection of HPoC. The increased expression of Apaf-1 and the downstream activation of capsase-3/9 after OGD were mitigated by HPoC or the addition of miR-183 mimetics, whereas miR-183 inhibitor diminished the effect of HPoC on Apaf-1-caspase signaling. In the in vivo experiment, iPoC and agomiR-183 decreased the expression of serum ALT after liver IR in the mice, but antagomiR-183 mitigated the effect of iPoC. The results of hematoxylin and eosin and TUNEL staining were compatible with the biochemical assay. Moreover, iPoC and agomiR-183 decreased the expression of Apaf-1 and 4-HNE after IR injury in mouse livers, whereas the antagomiR-mediated prevention of miR-183 expression led to increased protein expression of Apaf-1 and 4-HNE in the postischemic livers.
  
  
  
  Our experiment showed the first time that miR-183 was induced in protective postconditioning and reduced reperfusion injury of the livers via the targeting of apoptotic signaling.
  
  
  
  miR-183 mediated the tolerance induced by iPoC in livers via Apaf-1 repressing. Antioxid. Redox Signal. 26, 583-597.
authors: 1 Department of Anatomy and Cell Biology, Medical College, National Taiwan University , Taipei, Taiwan .|2 Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan .
authors: Han-Chen
authors: HC
authors: Lin
authors: 1 Department of Anatomy and Cell Biology, Medical College, National Taiwan University , Taipei, Taiwan .
authors: Shin-Yun
authors: SY
authors: Liu
authors: 1 Department of Anatomy and Cell Biology, Medical College, National Taiwan University , Taipei, Taiwan .
authors: Er-Yen
authors: EY
authors: Yen
authors: 3 Graduate Institute of Microbiology, Medical College, National Taiwan University , Taipei, Taiwan .
authors: Tsai-Kun
authors: TK
authors: Li
authors: 1 Department of Anatomy and Cell Biology, Medical College, National Taiwan University , Taipei, Taiwan .|4 Department of Surgery, National Taiwan University Hospital , Taipei, Taiwan .
authors: I-Rue
authors: IR
authors: Lai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D057775:Ischemic Postconditioning; D008099:Liver / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; C584645:MIRN183 microRNA, rat; D035683:MicroRNAs; C543802:Mirn183 microRNA, mouse; D005947:Glucose; D010100:Oxygen
keywords: hypoxic postconditioning; miR-183; oxygen-glucose deprivation