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Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke
Cell Death & Disease ( IF 9 ) Pub Date : 2021-01-06 , DOI: 10.1038/s41419-020-03310-2
Jin Yang 1 , Lu-Lu Cao 1, 2 , Xi-Peng Wang 1 , Wei Guo 1 , Ruo-Bing Guo 1 , Yu-Qin Sun 1 , Teng-Fei Xue 1 , Zhen-Yu Cai 1 , Juan Ji 1 , Hong Cheng 3 , Xiu-Lan Sun 1, 4
Affiliation  

Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.



中文翻译:

神经元细胞外囊泡衍生的 miR-98 可防止可挽救的神经元免受急性缺血性中风的小胶质细胞吞噬作用

细胞外囊泡(EVs)作为一种新型的细胞间通讯载体,可以转移货物 microRNAs(miRNAs),在缺血性中风后的大脑重塑过程中发挥重要作用。然而,EVs 衍生的 miRNAs 介导的大脑细胞相互作用的详细机制仍不清楚。多项研究表明,microRNA-98(miR-98)可能参与缺血性卒中的发病机制。在这里,我们发现 miR-98 在大鼠缺血性卒中后第一天保持不变,但在第 3 天急剧下降,表明 miR-98 可以作为缺血后的内源性保护因子。miR-98的过表达靶向抑制血小板激活因子受体介导的小胶质细胞吞噬作用以减轻神经元死亡。此外,我们发现神经元在缺血性中风后通过 EV 分泌将 miR-98 转移到小胶质细胞,以防止压力但有活力的神经元被小胶质细胞吞噬。因此,我们揭示了 EVs 衍生的 miR-98 在缺血性中风后的大脑重塑过程中充当介导神经元和小胶质细胞通讯的细胞间信号。目前的工作提供了对 EVs 在中风发病机制中的作用的新见解,以及一种新的基于 EVs-miRNAs 的中风治疗策略。

更新日期:2021-01-08
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