Down-Regulation of MicroRNA-146a in the Early Stage of Liver Ischemia-Reperfusion Injury

• DOI: 10.1016/j.transproceed.2012.10.045
• Publication Date: 2013-03-15T04:58:03Z
• Authors: Q. Chen; L. Kong; X. Xu; Q. Geng; W. Tang; W. Jiang
• Keywords: TNF Receptor-Associated Factor 6; 0301 basic medicine; 0303 health sciences; Time Factors; Interleukin-6; Proto-Oncogene Proteins c-jun; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha; Blotting, Western; Transcription Factor RelA; Down-Regulation; Alanine Transaminase; Real-Time Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Toll-Like Receptor 4; Disease Models, Animal; MicroRNAs; 03 medical and health sciences; Interleukin-1 Receptor-Associated Kinases; Liver; Reperfusion Injury; Animals

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.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.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.miR-146a was down-regulated in the early stage of liver IR injury.