Department of Critical Care Medicine, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.
Department of Intervention, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.
J Biochem Mol Toxicol. 2018 Apr;32(4):e22044. doi: 10.1002/jbt.22044. Epub 2018 Feb 19.
Accumulating evidence has reported that microRNA-144-3p (miR-144-3p) is highly related to oxidative stress and apoptosis. However, little is known regarding its role in cerebral ischemia/reperfusion-induced neuronal injury. Herein, our results showed that miR-144-3p expression was significantly downregulated in neurons following oxygen-glucose deprivation and reoxygenation (OGD/R) treatment. Overexpression of miR-144-3p markedly reduced cell viability, promoted cell apoptosis, and increased oxidative stress in neurons with OGD/R treatment, whereas downregulation of miR-144-3p protected neurons against OGD/R-induced injury. Brahma-related gene 1 (Brg1) was identified as a potential target gene of miR-144-3p. Moreover, downregulation of miR-144-3p promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased antioxidant response element (ARE) activity. However, knockdown of Brg1 significantly abrogated the neuroprotective effects of miR-144-3p downregulation. Overall, our results suggest that miR-144-3p contributes to OGD/R-induced neuronal injury in vitro through negatively regulating Brg1/Nrf2/ARE signaling.
越来越多的证据表明,微小 RNA-144-3p(miR-144-3p)与氧化应激和细胞凋亡密切相关。然而,miR-144-3p 在脑缺血/再灌注诱导的神经元损伤中的作用知之甚少。本研究结果表明,氧葡萄糖剥夺和复氧(OGD/R)处理后神经元中 miR-144-3p 表达明显下调。过表达 miR-144-3p 可显著降低 OGD/R 处理后神经元的细胞活力,促进细胞凋亡,增加氧化应激,而 miR-144-3p 的下调可保护神经元免受 OGD/R 诱导的损伤。Brahma 相关基因 1(Brg1)被鉴定为 miR-144-3p 的潜在靶基因。此外,下调 miR-144-3p 可促进核因子红细胞 2 相关因子 2(Nrf2)的核转位,并增加抗氧化反应元件(ARE)活性。然而,Brg1 的敲低显著削弱了 miR-144-3p 下调的神经保护作用。总之,我们的研究结果表明,miR-144-3p 通过负调控 Brg1/Nrf2/ARE 信号通路,促进体外 OGD/R 诱导的神经元损伤。