MicroRNA-378 protects against intestinal ischemia/reperfusion injury via a mechanism involving the inhibition of intestinal mucosal cell apoptosis

被引:69
作者
Li, Yunsheng [1 ,2 ]
Wen, Shihong [2 ]
Yao, Xi [3 ]
Liu, Weifeng [1 ]
Shen, Jiantong [2 ]
Deng, Wentao [1 ]
Tang, Jing [1 ]
Li, Cai [1 ]
Liu, Kexuan [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Anesthesiol, 1838 Guangzhou Ave North, Guangzhou 510515, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Anesthesiol, Guangzhou 510080, Guangdong, Peoples R China
[3] Shaanxi Prov Peoples Hosp, Dept Anesthesiol, Xian 710068, Shaanxi, Peoples R China
关键词
ISCHEMIA-REPERFUSION INJURY; ISCHAEMIA/REPERFUSION INJURY; TARGET PREDICTION; ALDOSE REDUCTASE; OXIDATIVE STRESS; RATS; EXPRESSION; CASPASE-3; GROWTH; DEATH;
D O I
10.1038/cddis.2017.508
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:e3127 / e3127
页数:11
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