Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
J Stroke Cerebrovasc Dis. 2022 Nov;31(11):106748. doi: 10.1016/j.jstrokecerebrovasdis.2022.106748. Epub 2022 Sep 7.
Toll-like receptor 4 (TLR4) plays a critical role in ischemic brain injury by mediating the inflammatory response. The microRNA miR-185-5p suppresses inflammatory signaling by targeting TLR4. This study investigates whether overexpressing miR-182-5p in bone marrow-derived mesenchymal stem cells (BM-MSCs) could potentiate the neuroprotective effects of BM-MSCs in a mouse model of ischemic brain injury.
We isolated BM-MSCs from mice, transfected the cells with miR-182-5p mimic, determined their MSC lineage through flow cytometry analysis of surface markers, examined miR-182-5p and TLR4 expression levels, and injected them into mice undergone middle cerebral artery occlusion (MCAO). MSC transplanted mice were subjected to behavior assays to determine cognitive and motor functions and biochemical analysis to determine neuroinflammation and TLR4/NF-κB in the ischemic hemisphere.
We found that BM-MSCs overexpressing miR-182-5p showed reduced TLR4 expression without affecting their MSC lineage. Mice transplanted with miR-182-5p overexpressing BM-MSCs after MCAO showed significantly improved cognitive and motor functions and reduced neuroinflammation, including suppressed microglial M1 polarization, reduced inflammatory cytokines, and inhibited TLR4/ NF-κB signaling.
Our findings suggest that overexpressing miR-182-5p in BM-MSCs can enhance the neuroprotective effects of BM-MSCs against ischemic brain injury by suppressing TLR4-mediated inflammatory response.
Toll 样受体 4（TLR4）通过介导炎症反应在缺血性脑损伤中发挥关键作用。miR-185-5p 通过靶向 TLR4 抑制炎症信号。本研究探讨了在骨髓间充质干细胞（BM-MSCs）中过表达 miR-182-5p 是否可以增强 BM-MSCs 在缺血性脑损伤小鼠模型中的神经保护作用。
我们从小鼠中分离 BM-MSCs，用 miR-182-5p 模拟物转染细胞，通过流式细胞术分析表面标志物确定 MSC 谱系，检测 miR-182-5p 和 TLR4 的表达水平，并将其注射到大脑中动脉闭塞（MCAO）的小鼠中。接受 MSC 移植的小鼠进行行为学测定以确定认知和运动功能，并进行生化分析以确定缺血半球的神经炎症和 TLR4/NF-κB。
我们发现过表达 miR-182-5p 的 BM-MSCs 表现出 TLR4 表达降低，而不影响其 MSC 谱系。MCAO 后接受过表达 miR-182-5p 的 BM-MSCs 移植的小鼠表现出明显改善的认知和运动功能，以及减少的神经炎症，包括抑制小胶质细胞 M1 极化、减少炎症细胞因子和抑制 TLR4/NF-κB 信号。
我们的研究结果表明，在 BM-MSCs 中过表达 miR-182-5p 可以通过抑制 TLR4 介导的炎症反应来增强 BM-MSCs 对缺血性脑损伤的神经保护作用。
