The delivery of miR-21a-5p by extracellular vesicles induces microglial polarization via the STAT3 pathway following hypoxia-ischemia in neonatal mice  

作　　者：Dan-Qing Xin Yi-Jing Zhao Ting-Ting Li Hong-Fei Ke Cheng-Cheng Gai Xiao-Fan Guo Wen-Qiang Chen De-Xiang Liu Zhen Wang 

机构地区：[1]Department of Physiology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China [2]Department of Neurology,Loma Linda University Health,Loma Linda,CA,USA [3]Department of Cardiology,Qilu Hospital,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China [4]Department of Medical Psychology and Ethics,School of Basic Medicine Sciences,Cheeloo College of Medicine,Shandong University,Jinan,Shandong Province,China

出　　处：《Neural Regeneration Research》2022年第10期2238-2246,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81873768,82072535,81671213(to ZW),81770436(to WQC);the National Key Project of Chronic Non-Communicable Disease of China,No.2016YFC1300403(to WQC).

摘　　要：Extracellular vesicles(EVs)from mesenchymal stromal cells(MSCs)have previously been shown to protect against brain injury caused by hypoxia-ischemia(HI).The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs.However,the underlying mechanisms have not previously been determined.In this study,we induced oxygen-glucose deprivation in BV-2 cells(a microglia cell line),which mimics HI in vitro,and found that treatment with MSCs-EVs increased the cell viability.The treatment was also found to reduce the expression of pro-inflammatory cytokines,induce the polarization of microglia towards the M2 phenotype,and suppress the phosphorylation of selective signal transducer and activator of transcription 3(STAT3)in the microglia.These results were also obtained in vivo using neonatal mice with induced HI.We investigated the potential role of miR-21a-5p in mediating these effects,as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway.We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells,which had been lowered following oxygen-glucose deprivation.When the level of miR-21a-5p in the MSCs-EVs was reduced,the effects on microglial polarization and STAT3 phosphorylation were reduced,for both the in vitro and in vivo HI models.These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p,which induces microglial M2 polarization by targeting STAT3.

关 键 词：extracellular vesicles HYPOXIA-ISCHEMIA mesenchymal stromal cells MICROGLIA miR-21a-5p NEUROINFLAMMATION oxygen-glucose deprivation STAT3 

分 类 号：R741[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]