The microRNA-146a/b attenuates acute small-for-size liver graft injury in rats
The microRNA-146a/b attenuates acute small-for-size liver graft injury in rats
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MicroRNA-146a/b 可减轻大鼠急性小尺寸肝移植损伤
DOI：
10.1111/liv.12674
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发表时间：
2015-03-01
影响因子：
6.7
通讯作者：
Kong, Lianbao
中科院分区：
文献类型：
--
作者：
Jiang, Weiwei;Ni, Qingfeng;Kong, Lianbao
背景与目的Toll样受体（TLR）-4及其下游介质在小体积移植肝损伤的发病机制中起着关键作用。最近，microRNA-146（miR-146）被鉴定为TLR 4信号通路的有效负调节剂。在这项研究中，miR-146 a和miR-146 b的TLR-4信号和small-for-size肝移植injury的衰减的作用进行了investigated.MethodsThe miR-146 a和miR-146 b的表达水平在small-for-size肝移植injury在体内进行了研究。此外，在体外研究了miR-146 a和miR-146 b对大鼠巨噬细胞系NR 8383和大鼠肝枯否细胞中IRAK 1和TRAF 6表达的影响。通过尾静脉注射miR-146 a模拟物和miR-146 b模拟物，研究miR-146 a和miR-146 b对小体积肝移植损伤的体内作用。在大鼠巨噬细胞系NR 8383中，miR-146 a和miR-146 b分别通过与IRAK 1或TRAF 6的3UTR结合来抑制IRAK 1和TRAF 6的表达。miR-146 a和miR-146 b通过抑制IRAK 1和TRAF 6的表达，在小体积肝移植物损伤中预防肝损伤。结论miR-146 a和miR-146 b通过抑制IRAK 1和TRAF 6的表达，在小体积肝移植物损伤中预防肝损伤。
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.