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Neuroprotective effects of miR-532-5p against ischemic stroke.
Metabolic Brain Disease ( IF 3.2 ) Pub Date : 2020-02-21 , DOI: 10.1007/s11011-020-00544-z
Jingwei Mu 1, 2 , Xi Cheng 1 , Shanshan Zhong 1 , Xiaohong Chen 2 , Chuansheng Zhao 1
Affiliation  

Stroke can cause death and disability and has a high incidence with many complications. So far, effective treatment options for stroke are still limited. MicroRNA-532-5p (miR-532-5p) is significantly downregulated in stroke. However, the role of miR-532-5p in ischemic stroke is still unclear. In this study, we established an in vivo middle cerebral artery occlusion (MCAO) model in mice. The expression level of miR-532-5p, neurological score, infarct area, neuronal apoptosis, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway-related molecules were examined. Low miR-532-5p levels and high phosphatase and tensin homolog deleted on chromosome 10 (PTEN) levels were detected in the mouse MCAO model. MiR-532-5p overexpression improved neurological dysfunction, reduced the infarct area, attenuated neuronal injury and apoptosis, and promoted the activation of the PI3K/Akt signaling pathway in MCAO mice. In vitro, we treated mouse neuroblastoma cells (N2a) with oxygen-glucose deprivation and reperfusion (OGD/R). The expression level of miR-532-5p, cell viability, cell apoptosis, and the PI3K/Akt signaling pathway-related molecules were detected. Consistent with the in vivo tests, the miR-532-5p level was decreased and the PTEN level was increased in OGD-treated N2a cells in vitro. The miR-532-5p mimic increased cell viability, decreased cell apoptosis, and activated the PI3K/Akt signaling pathway. Furthermore, PTEN was verified as a target gene of miR-532-5p by luciferase reporter assay. PTEN overexpression attenuated the protective effect of miR-532-5p in OGD-treated N2a cells. In summary, these findings reveal that miR-532-5p protects against ischemic stroke by inhibiting PTEN and activating the PI3K/Akt signaling pathway and may serve as a novel therapeutic target for ischemic stroke.

中文翻译:

miR-532-5p 对缺血性中风的神经保护作用。

中风可导致死亡和残疾,发病率高,并发症多。迄今为止,中风的有效治疗选择仍然有限。MicroRNA-532-5p (miR-532-5p) 在中风中显着下调。然而,miR-532-5p 在缺血性卒中中的作用尚不清楚。在这项研究中,我们建立了小鼠体内大脑中动脉闭塞(MCAO)模型。检查了 miR-532-5p、神经系统评分、梗死面积、神经元凋亡和磷酸肌醇 3-激酶 (PI3K)/Akt 信号通路相关分子的表达水平。在小鼠 MCAO 模型中检测到低 miR-532-5p 水平以及在 10 号染色体 (PTEN) 水平上缺失的高磷酸酶和张力蛋白同源物。MiR-532-5p 过表达改善神经功能障碍,减少梗塞面积,减轻神经元损伤和细胞凋亡,并促进 MCAO 小鼠 PI3K/Akt 信号通路的激活。在体外,我们用氧-葡萄糖剥夺和再灌注 (OGD/R) 处理小鼠神经母细胞瘤细胞 (N2a)。检测miR-532-5p的表达水平、细胞活力、细胞凋亡和PI3K/Akt信号通路相关分子的表达。与体内试验一致,在体外OGD处理的N2a细胞中,miR-532-5p水平降低而PTEN水平升高。miR-532-5p 模拟物增加细胞活力,减少细胞凋亡,并激活 PI3K/Akt 信号通路。此外,通过荧光素酶报告基因检测证实 PTEN 是 miR-532-5p 的靶基因。PTEN 过表达减弱了 miR-532-5p 在 OGD 处理的 N2a 细胞中的保护作用。总之,
更新日期:2020-02-21
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