Tle1 attenuates hepatic ischemia/reperfusion injury by suppressing NOD2/NF-κB signaling
Tle1 attenuates hepatic ischemia/reperfusion injury by suppressing NOD2/NF-κB signaling
复制标题
Tle1 通过抑制 NOD2/NF-κB 信号传导减轻肝缺血/再灌注损伤
DOI：
10.1080/09168451.2020.1735928
复制
发表时间：
2020-03-02
影响因子：
1.6
通讯作者：
Wu, Zhongjun
中科院分区：
文献类型：
--
作者：
Chen, Wei;Zheng, Daofeng;Wu, Zhongjun
ABSTRACT Liver damage induced by ischemia/reperfusion (I/R) remains a primary issue in multiple hepatic surgeries. Innate immune-mediated inflammatory responses during the reperfusion stage aggravate the injury. Nevertheless, the detailed mechanism of hepatic I/R has not been fully clarified yet. Our research focuses on the role of Transducin-like enhancer of split-1 (Tle1) in the liver I/R injury and the relation between Tle1 and Nucleotide-binding oligomerization domain 2 (NOD2). To answer these questions, we constructed mouse models of I/R and cell models of hypoxia/reoxygenation (H/R). We found decreased Tle1 accompanied by increased NOD2 during reperfusion. Mice pro-injected with Tle1-siRNA emerged aggravated liver dysfunction. Repression of Tle1 had a significant impact on NOD2 and downstream NF-κB signaling in vitro. However, alteration of NOD2 failed to affect the expression of Tle1. To conclude, our study demonstrates that Tle1 shelters the liver from I/R injury through suppression of NOD2-dependent NF-κB activation and subsequent inflammatory responses. Graphical abstract During the hepatic ischemia/reperfusion injury, Tle1 reduces inflammation by regulating the NOD2/NF-κB signaling pathway.
