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.

中文翻译：

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Tle1通过抑制NOD2 /NF-κB信号传导减轻肝脏缺血/再灌注损伤。

缺血/再灌注（I / R）引起的肝损伤仍然是多个肝脏手术中的主要问题。在再灌注阶段先天免疫介导的炎症反应加剧了损伤。然而，肝I / R的详细机制尚未完全阐明。我们的研究集中在肝脏I / R损伤中，split-1的转导蛋白样增强子（Tle1）的作用以及Tle1与核苷酸结合寡聚域2（NOD2）之间的关系。为了回答这些问题，我们构建了I / R小鼠模型和缺氧/复氧（H / R）细胞模型。我们发现再灌注过程中Tle1降低，NOD2增加。预注射Tle1-siRNA的小鼠出现了肝功能异常加重。在体外，Tle1的抑制对NOD2和下游NF-κB信号传导有重要影响。然而，NOD2的变化不能影响Tle1的表达。总而言之，我们的研究表明，Tle1通过抑制NOD2依赖性NF-κB活化和随后的炎症反应，使肝脏免受I / R损伤。