Ji Qiong, Gao Jianbo, Zheng Yan, Liu Xueli, Zhou Qiangqiang, Shi Canxia, Yao Meng, Chen Xia
Department of Pharmacology, College of Basic Medical Science, Jilin University, Changchun, Jilin, 130021, People's Republic of China.
Department of Neonatology, Frist Hospital of Jilin University, Changchun, Jilin, 130021, People's Republic of China.
J Biochem Mol Toxicol. 2017 Jul;31(7). doi: 10.1002/jbt.21905. Epub 2017 Feb 28.
MicroRNAs are emerging as critical regulators in cerebral ischemia/reperfusion injury; however, their exact roles remain poorly understood. miR-153 is reported to be a neuron-related miRNA involved in neuroprotection. In this study, we aimed to investigate the precise role of miR-153 in regulating neuron survival during cerebral ischemia/reperfusion injury using an oxygen-glucose deprivation and reoxygenation (OGD/R) cellular model. We found that miR-153 was significantly upregulated in neurons subjected to OGD/R treatment. Inhibition of miR-153 significantly attenuated OGD/R-induced injury and oxidative stress in neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as a target gene of miR-153. Inhibition of miR-153 significantly promoted the expression of Nrf2 and heme oxygenase-1 (HO-1). However, silencing of Nrf2 significantly blocked the protective effects of miR-153 inhibition. Our study indicates that the inhibition of miR-153 protects neurons against OGD/R-induced injury by regulating Nrf2/HO-1 signaling and suggests a potential therapeutic target for cerebral ischemia/reperfusion injury.
微小RNA正成为脑缺血/再灌注损伤的关键调节因子；然而，它们的确切作用仍知之甚少。据报道，miR-153是一种参与神经保护的神经元相关微小RNA。在本研究中，我们旨在使用氧-葡萄糖剥夺和复氧（OGD/R）细胞模型，研究miR-153在脑缺血/再灌注损伤期间调节神经元存活的确切作用。我们发现，在接受OGD/R处理的神经元中，miR-153显著上调。抑制miR-153可显著减轻OGD/R诱导的神经元损伤和氧化应激。核因子红细胞2相关因子2（Nrf2）被确定为miR-153的靶基因。抑制miR-153可显著促进Nrf2和血红素加氧酶-1（HO-1）的表达。然而，沉默Nrf2可显著阻断miR-153抑制的保护作用。我们的研究表明，抑制miR-153通过调节Nrf2/HO-1信号通路保护神经元免受OGD/R诱导的损伤，并提示脑缺血/再灌注损伤的潜在治疗靶点。
