Down-regulation of IFIT3 protects liver from ischemia-reperfusion injury
Down-regulation of IFIT3 protects liver from ischemia-reperfusion injury
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下调 IFIT3 可保护肝脏免受缺血再灌注损伤
DOI：
10.1016/j.intimp.2018.04.045
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发表时间：
2018-07-01
影响因子：
5.6
通讯作者：
Zang, Yunjin
中科院分区：
文献类型：
--
作者：
Guan, Ge;Shen, Yuntai;Zang, Yunjin
肝脏缺血再灌注损伤（IRI）是肝脏手术和移植过程中严重的肝脏损伤和功能障碍。IFIT 3作为干扰素（IFN）刺激基因之一，具有抗肿瘤活性，但其在肝脏IRI中的作用尚不清楚。在这项研究中，IFIT 3在肝脏IRI的作用进行了研究，使用小鼠肝脏IRI模型和细胞缺氧-复氧模型。首先，我们的研究结果表明，IFIT 3在肝移植患者再灌注肝组织中上调，并与血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）正相关。第二，在体内和体外，IFIT 3基因的敲低可以显著改善肝脏IRI，抑制缺血再灌注诱导的炎症细胞因子的释放。此外，在体内和体外，IFIT 3的敲低抑制STAT 1和STAT 2的磷酸化，并降低由缺血和再灌注诱导的IFN刺激基因的表达。这些数据突出了IFIT 3在肝IRI中的重要性和潜在临床用途。
Hepatic ischemia-reperfusion injury (IRI) could result in severe liver damage and dysfunction during liver surgery and transplantation. As one of the Interferon (IFN)-stimulated genes, IFIT3 exerted antitumor activity but its roles in hepatic IRI are still unknown. In this study, roles of IFIT3 in hepatic IRI were investigated using a mouse hepatic IRI model and a cellular hypoxia-reoxygenation model. Firstly, our results showed that IFIT3 was up-regulated in reperfused liver tissues of patients undergoing liver transplantation and was positively correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Secondly, knockdown of IFIT3 could significantly ameliorate hepatic IRI and suppress ischemia and reperfusion-induced release of inflammatory cytokines in vivo and in vitro. Furthermore, knockdown of IFIT3 inhibited phosphorylation of STAT1 and STAT2, and decreased expressions of IFN-stimulated genes induced by ischemia and reperfusion in vivo and in vitro. These data highlight the importance and potential clinical use of IFIT3 in hepatic IRI.