MicroRNA-378 protects against intestinal ischemia/reperfusion injury via a mechanism involving the inhibition of intestinal mucosal cell apoptosis.
MicroRNA-378 protects against intestinal ischemia/reperfusion injury via a mechanism involving the inhibition of intestinal mucosal cell apoptosis.
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MicroRNA-378 通过抑制肠粘膜细胞凋亡的机制预防肠缺血/再灌注损伤
DOI：
10.1038/cddis.2017.508
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发表时间：
2017-10-12
影响因子：
9
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Li Y;Wen S;Yao X;Liu W;Shen J;Deng W;Tang J;Li C;Liu K
肠缺血/再灌注（I/R）损伤仍然是一个主要的临床事件，并导致高发病率和死亡率，但其潜在的机制仍然是难以捉摸的。近年来的研究表明，microRNAs（miRNAs）在器官I/R损伤中发挥重要作用，但miRNAs在肠I/R损伤中的变化及其潜在作用尚不清楚。本研究旨在分析肠I/R损伤后肠黏膜中miRNA的表达谱，并探讨靶miRNA在此过程中的作用。利用miRNA微阵列分析，我们从肠I/R小鼠模型的miRNA表达谱中发现了19个miRNA的变化，并通过RT-qPCR进一步验证。在这里，我们报告说，miR-378是显着减少的miRNA之一，并在应用TargetScan、米兰达、CLIP-Seq和miRDB预测算法后发现了与细胞死亡相关的推定靶mRNA。我们的研究结果表明，miR-378的过表达显著改善了野生型和转基因小鼠的肠组织损伤以及氧葡萄糖剥夺/再灌注挑战的IEC-6细胞损伤。此外，在体内和体外缺血模型中，miR-378过表达减少肠上皮细胞凋亡，并减弱切割的caspase-3表达。总的来说，我们的研究结果表明，抑制caspase-3激活的miRNA-378过表达可能参与肠缺血性损伤的保护作用。miRNA-378可能是肠I/R损伤的关键调节因子和治疗靶点。
Intestinal ischemia/reperfusion (I/R) injury remains a major clinical event and contributes to high morbidity and mortality rates, but the underlying mechanisms remain elusive. Recent studies have demonstrated that microRNAs (miRNAs) have important roles in organ I/R injury, but the changes and potential roles of miRNAs in intestinal I/R-induced intestinal injury are unclear. This study was designed to analyze the miRNA expression profiles in intestinal mucosa after I/R injury and to explore the role of target miRNA during this process. Using miRNA microarray analysis, we found changes of 19 miRNAs from the expression profile of miRNAs in a mouse model of intestinal I/R and further verified them by RT-qPCR. Here, we report that miR-378 is one of the markedly decreased miRNAs and found the putative target mRNA that is linked to cell death after applying the TargetScan, miRanda, CLIP-Seq and miRDB prediction algorithms. Our results show that the overexpression of miR-378 significantly ameliorated intestinal tissue damage in wild-type and transgenic mice and oxygen glucose deprivation/reperfusion-challenged IEC-6 cell injury. Moreover, miR-378 overexpression reduced intestinal epithelial cell apoptosis in both in vivo and in vitro ischemic models and attenuated cleaved caspase-3 expression. Collectively, our results revealed that the suppression of caspase-3 activation by miRNA-378 overexpression may be involved in the protective effects of intestinal ischemic damage. MiRNA-378 may serve as a key regulator and therapeutic target in intestinal I/R injury.
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