期刊
LIVER INTERNATIONAL
卷 35, 期 3, 页码 914-924出版社
WILEY-BLACKWELL
DOI: 10.1111/liv.12674
关键词
IL-1 receptor-associated kinase 1; miR-146; small-for-size liver graft; Toll-like receptor 4; tumour necrosis factor receptor-associated factor 6
资金
- National Natural Science Foundation of China [81100318, 81270483]
Background & AimsA critical role of the Toll-like receptor (TLR)-4 and its downstream mediators in the pathogenesis of small-for-size liver graft injury has been documented. Recently, the microRNA-146 (miR-146) was identified as a potent negative regulator of the TLR4 signalling pathway. In this study, the role of miR-146a and miR-146b in the attenuation of TLR-4 signalling and small-for-size liver graft injury was investigated. MethodsThe expression levels of miR-146a and miR-146b during small-for-size liver graft injury were studied in vivo. In addition, the effects of miR-146a and miR-146b on the expression of IRAK1 and TRAF6 in the rat macrophage cell line NR8383 and rat liver kupffer cells were studied in vitro. The in vivo effect of miR-146a and miR-146b on small-for-size liver graft injury was studied by the tail vein injection of miR-146a mimics and miR-146b mimics. ResultsThe levels of miR-146a and miR-146b decreased with a small-for-size liver graft. MiR-146a and miR-146b inhibited IRAK1 and TRAF6 expression by binding to the 3UTR of IRAK1 or TRAF6, respectively, in the rat macrophage cell line NR8383. The administration of miR-146a mimics and miR-146b mimics prevented liver graft injury in small-for-size liver graft injury via the inactivation of IRAK1 and TRAF6 in vivo. ConclusionsmiR-146a and miR-146b prevent liver injury in small-for-size liver graft injury via the inactivation of IRAK1 and TRAF6.
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