title: MicroRNA-182-5p Ameliorates Liver Ischemia-Reperfusion Injury by Suppressing Toll-Like Receptor 4.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) has received a lot of attention in studies on ischemia-reperfusion (I/R) injury. TLR4 is one of the target genes for microRNA-182-5p (miR-182-5p)-mediated regulation. In this study, we evaluated the role(s) of miR-182-5p transcriptional regulation in a hepatic I/R injury model in vivo and a lipopolysaccharide (LPS)-induced inflammatory reaction model in vitro.
  
  
  METHODS
  The effects of miR-182-5p expression on the transcription and translation of TLR4 and several proinflammatory cytokines in a LPS-induced macrophage model were studied in vitro. After miR-182-5p was exogenously administered, the transcriptional/translational profile of TLR4 and the proinflammatory cytokines were evaluated in an in vivo I/R injury model. This data were combined with alanine transaminase expression levels and histologic features in an effort to understand the role(s) of miR-182-5p in a liver I/R model.
  
  
  RESULTS
  TLR4 mRNA and protein levels in LPS-induced macrophages were significantly decreased in the presence of miR-182-5p (P < .01). In vivo TLR4 mRNA and protein levels as well as the induction of several proinflammatory cytokines, including tumor necrosis factor α and interleukin-6, were decreased in the presence of miR-182-5p. Hematoxylin and eosin staining showed that edema and necrosis in I/R modes were alleviated in the miR-182-5p-expressing group compared with control.
  
  
  CONCLUSIONS
  miR-182-5p attenuates hepatic I/R by directly suppressing TLR4.
authors: Department of Neonatal Surgery, Children's Hospital of Nanjing Medical University, Nanjing, People's Republic of China. Electronic address: wwjiang@njmu.edu.cn.
authors: W
authors: W
authors: Jiang
authors: Department of Neonatal Surgery, Children's Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors: G
authors: G
authors: Liu
authors: Department of Neonatal Surgery, Children's Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors: W
authors: W
authors: Tang
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D035683:MicroRNAs; C578934:Mirn185 microRNA, mouse; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse