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通过靶向EIF4G2,抑制miR-379-5P可增强缺血/再灌注后肠上皮细胞增殖及屏障功能恢复。

miR-379-5P INHIBITION ENHANCES INTESTINAL EPITHELIAL PROLIFERATION AND BARRIER FUNCTION RECOVERY AFTER ISCHEMIA/REPERFUSION BY TARGETING EIF4G2.

作者信息

Jia Zirui, Wang Yuhang, Gao Jiacheng, Zheng Mingcan, Wang Puxu, Zu Guo

机构信息

Department of Gastrointestinal Surgery, The Dalian Municipal Central Hospital Affiliated to Dalian Medical University, Dalian, China.

出版信息

Shock. 2023 Oct 1;60(4):594-602. doi: 10.1097/SHK.0000000000002205. Epub 2023 Aug 22.

Abstract

Gut barrier dysfunction caused by intestinal ischemia/reperfusion (I/R) injury is associated with substantial death and morbidity. In this research, the role of microRNAs (miRNAs) in regulating intestinal I/R injury was investigated. We used miRNA sequencing to analyze clinical ischemic and normal intestinal samples. Through bioinformatics analysis based on sequencing results, we found that upregulated miRNAs inhibited epithelial barrier function and cell proliferation, with miR-379-5p being the most significantly upregulated in the ischemic intestine. Further studies confirmed the role of miR-379-5p through experiments in the human ischemic intestine, the mouse I/R injury model in vivo , and cell hypoxia/reoxygenation models in vitro . Inhibiting miR-379-5p increased epithelial cell proliferation and improved barrier function after I/R injury. We also identified eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) as a downstream target gene of miR-379-5p through bioinformatics prediction and experimental verification. The findings suggest that inhibiting miR-379-5p could improve intestinal epithelial cell proliferation and barrier function by targeting EIF4G2. The goal of this study was to find a potential target for treating I/R injury in the intestine, as well as to prevent and mitigate the damage caused.

摘要

肠道缺血/再灌注(I/R)损伤引起的肠道屏障功能障碍与大量死亡和发病相关。在本研究中,研究了微小RNA(miRNA)在调节肠道I/R损伤中的作用。我们使用miRNA测序分析临床缺血性和正常肠道样本。通过基于测序结果的生物信息学分析,我们发现上调的miRNA抑制上皮屏障功能和细胞增殖,其中miR-379-5p在缺血性肠道中上调最为显著。进一步的研究通过在人缺血性肠道、小鼠体内I/R损伤模型和体外细胞缺氧/复氧模型中的实验证实了miR-379-5p的作用。抑制miR-379-5p可增加I/R损伤后上皮细胞增殖并改善屏障功能。我们还通过生物信息学预测和实验验证确定真核翻译起始因子4γ2(EIF4G2)为miR-379-5p的下游靶基因。这些发现表明,抑制miR-379-5p可通过靶向EIF4G2改善肠道上皮细胞增殖和屏障功能。本研究的目的是找到治疗肠道I/R损伤的潜在靶点,以及预防和减轻所造成的损伤。

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