title: Down-regulation of microRNA-146a in the early stage of liver ischemia-reperfusion injury.
abstract: BACKGROUND
  MicroRNAs (miRNAs), 21-23-nucleotide noncoding RNAs, act as regulators of gene expression transcriptionally. MicroRNA-146a(miR-146a) has been demonstrated to be one of the key molecules in oncogenesis and inflammatory responses. Few data describe the expression of miR-146a in liver ischemia-reperfusion (IR) injury. The present study sought to explore the relationship of miR-146a to Toll-like receptor 4 (TLR4) signaling pathways in a rat model of warm IR injury.
  
  
  METHODS
  The expression of miR-146a was detected by real-time reverse-transcriptase polymerase chain reaction using a partial warm hepatic IR injury model. The expression of TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6), and interleukin-1 receptor-associated kinase (IRAK 1) protein was assessed by Western blotting as well as the signaling pathways induced by TLR4.
  
  
  RESULTS
  The expression of hepatic miR-146a was down-regulated in IR injury during the 24 hours after reperfusion, reaching the lowest level at 6 hours after reperfusion. Increases in TLR4, TRAF6, and IRAK1 were accompanied by decreased miR-146a during the 24 hours after reperfusion, peaking at 6 hours. Immunohistochemistry showed cytoplasmic expression of cells positive for TLR4, and nuclear expression of cells positive for nuclear factor κB p65 and c-jun to be increased among IR groups after reperfusion.
  
  
  CONCLUSIONS
  miR-146a was down-regulated in the early stage of liver IR injury.
authors.affiliation: Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Kong
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: Q
authors.initials: Q
authors.lastname: Geng
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: W
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D015850:Interleukin-6; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun; C498145:Rela protein, rat; D048029:TNF Receptor-Associated Factor 6; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases