Recent studies have shown that the level of miR-1202 in peripheral blood is closely related to brain activity and cognitive function in patients with depression, and it is involved in glioma pathological progress. However, the correlation between miR-1202 and neuroinflammation has not been reported. The expressions of miR-1202 and small GTP-ase Rab1a at mRNA level were detected in oxygen-glucose deprivation (OGD)/reoxygenation (R) induced human microglial cells (HM cells) by RT-qPCR at different time points within 48 h. Dual luciferase report assay and immunofluorescence staining were performed to confirm whether Rab1a was the potential target of miR-1202. The toll-like receptor 4 (TLR4)/nuclear factor kappa beta (NF-κB) signal related proteins (TLR4, P65, p-P65, IκBa) and the downstream pro-inflammation factors pro-IL-1β, pro-IL-18, as well as the inflammation factors interleukin-1β (IL-1β) and interleukin-18 (IL-18) were detected by western-blotting. The expression level of TLR4 on cell surface was detected by flow cytometry. Down-regulation of miR-1202 and up-regulation of Rab1a were found in OGD/R induced HM cells. In addition, miR-1202 was identified to directly target Rab1a and down-regulate its expression. Moreover, over-expression of miR-1202 suppressed the activation of TLR4/NF-κB inflammatory signaling pathway. Rab1a can increase the expression level of TLR4 on the surface of OGD/R induced HM cells. MiR-1202 exerts neuroprotective effect by negatively regulating its target protein Rab1a, which can inactivate TLR4/NF-κB-involved inflammatory signaling pathway in OGD/R induced HM cells. These findings provide potential therapeutic targets for ischemic stroke.

中文翻译：

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MiR-1202通过负调控TLR4 /NF-κB信号通路所涉及的Rab1a，对OGD / R诱导的HM细胞炎症发挥神经保护作用。

最近的研究表明，抑郁症患者外周血中miR-1202的水平与脑活动和认知功能密切相关，并且与神经胶质瘤的病理进展有关。但是，尚未报道miR-1202与神经炎症之间的相关性。通过RT-qPCR，在48 h内的不同时间点，通过氧-葡萄糖剥夺（OGD）/复氧（R）诱导的人小胶质细胞（HM细胞）检测到miR-1202和小的GTP酶Rab1a在mRNA水平的表达。进行双重荧光素酶报告测定和免疫荧光染色以确认Rab1a是否是miR-1202的潜在靶标。Toll样受体4（TLR4）/核因子κB（NF-κB）信号相关蛋白（TLR4，P65，p-P65，IκBa）和下游促炎因子pro-IL-1β，pro-IL- 18岁 Western blotting检测出炎症因子IL-1β（IL-1β）和IL-18（IL-18）。通过流式细胞术检测TLR4在细胞表面的表达水平。在OGD / R诱导的HM细胞中发现miR-1202的下调和Rab1a的上调。此外，已确定miR-1202直接靶向Rab1a并下调其表达。此外，miR-1202的过表达抑制了TLR4 /NF-κB炎症信号通路的激活。Rab1a可以增加OGD / R诱导的HM细胞表面TLR4的表达水平。MiR-1202通过负调节其靶蛋白Rab1a发挥神经保护作用，该蛋白可灭活OGD / R诱导的HM细胞中TLR4 /NF-κB涉及的炎症信号通路。这些发现为缺血性中风提供了潜在的治疗靶点。