Shi Fangkun, Dong Zhiling, Li Hualian, Liu Xiaoman, Liu Hongmei, Dong Ruifang
Department of Neurology, Cangzhou Central Hospital, Cangzhou, China.
Department of Neurology, Cangzhou Central Hospital, Cangzhou, China.
Exp Cell Res. 2017 Mar 1;352(1):1-8. doi: 10.1016/j.yexcr.2017.01.015. Epub 2017 Jan 26.
MicroRNAs (miRNAs) have emerged as novel regulators in various pathological processes including ischemic stroke. However, the precise role of miRNAs in ischemic stroke remains largely unknown. In this study, we investigated the role of miR-137 in the regulation of neuronal ischemia/reperfusion injury with oxygen-glucose deprivation and reoxygenation (OGD/R), a model of global brain ischemia. The results showed that miR-137 was significantly downregulated in neurons subjected to OGD/R treatment: OGD/R-induced cell injury was markedly inhibited by miR-137 overexpression and exacerbated by miR-137 suppression. Moreover, Notch1 was predicted as a target gene of miR-137 and verified by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and western blot analysis. Through targeting of Notch1, miR-137 regulated the Notch signaling pathway. The blockade of the Notch signaling pathway reversed the effect of miR-137 suppression, whereas overexpression of the Notch intracellular domain abrogated the effect of miR-137 overexpression on OGD/R-induced cell injury. Overall, our study suggests that miR-137 regulated the Notch signaling pathway by targeting Notch1 to protect neurons from OGD/R-induced cell injury, providing a novel insight into understanding the molecular basis of ischemia stroke and a potential therapeutic target.
微小RNA(miRNA)已成为包括缺血性中风在内的各种病理过程中的新型调节因子。然而,miRNA在缺血性中风中的确切作用仍 largely unknown。在本研究中,我们研究了miR-137在以氧-葡萄糖剥夺和复氧(OGD/R)为模型的全脑缺血中对神经元缺血/再灌注损伤的调节作用。结果表明,在接受OGD/R处理的神经元中,miR-137显著下调:miR-137过表达显著抑制了OGD/R诱导的细胞损伤,而miR-137抑制则使其加剧。此外,Notch1被预测为miR-137的靶基因,并通过双荧光素酶报告基因检测、实时定量聚合酶链反应和蛋白质印迹分析得到验证。通过靶向Notch1,miR-137调节Notch信号通路。Notch信号通路的阻断逆转了miR-137抑制的作用,而Notch细胞内结构域的过表达则消除了miR-137过表达对OGD/R诱导的细胞损伤的影响。总体而言,我们的研究表明,miR-137通过靶向Notch1调节Notch信号通路,从而保护神经元免受OGD/R诱导的细胞损伤,为理解缺血性中风的分子基础提供了新的见解,并为潜在的治疗靶点提供了依据。