RETRACTED: Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction (Retracted Article)

被引:138
作者
Cai, Guofeng [1 ]
Cai, Guoliang [2 ,3 ]
Zhou, Haichun [1 ]
Zhuang, Zhe [1 ]
Liu, Kai [1 ]
Pei, Siying [1 ]
Wang, Yanan [1 ]
Wang, Hong [1 ]
Wang, Xin [1 ]
Xu, Shengnan [4 ]
Cui, Cheng [4 ]
Sun, Manchao [4 ]
Guo, Sihui [4 ]
Jia, Kunping [1 ]
Wang, Xiuzhen [1 ]
Zhang, Dianquan [5 ]
机构
[1] Heilongjiang Univ Tradit Chinese Med, Affiliated Hosp 2, Hanan Branch, Harbin 150001, Peoples R China
[2] Harbin Sport Univ, Postdoctoral Res Workstn, Harbin, Peoples R China
[3] Harbin Sport Univ, Dept Sport Sci & Hlth, Harbin 150008, Peoples R China
[4] Heilongjiang Univ Tradit Chinese Med, Harbin 150001, Peoples R China
[5] Shenzhen Longhua Dist Cent Hosp, Dept Rehabil Med, Shenzhen, Guangdong, Peoples R China
关键词
Cerebral infarction; Inflammation; Exosome; MicroRNA; MSC;
D O I
10.1186/s13287-020-02030-w
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
BackgroundCerebral infarction ranks as the second leading cause of disability and death globally, and inflammatory response of glial cells is the main cause of brain damage during cerebral infarction.MethodsStudies have shown that mesenchymal stem cells (MSCs) can secrete exosomes and contribute to cerebral disease. Here, we would explore the function of MSC-derived exosome in cerebral infarction.ResultsMicroarray indicated a decrease of miR-542-3p and an increase of Toll-Like Receptor 4 (TLR4) in middle cerebral artery occlusion (MCAO) mice comparing with sham mice. And luciferase and RIP analysis indicated a binding of miR-542-3p and TLR4. Then, we injected AAV9-miR-542-3p into paracele of sham or MCAO mice. Functional analysis showed that AAV9-miR-542-3p inhibited infarction area and the number of degenerating neurons and suppressed inflammatory factors' expression and inflammatory cell infiltration. As well, transfection of miR-542-3p mimics into HA1800 cells underwent oxygen and glucose deprivation (OGD). Similarly, overexpression of miR-542-3p alleviated OGD induced cell apoptosis, ROS, and activation of inflammation response. Moreover, miR-542-3p could be packaged into MSCs and secreted into HA1800 cells. The extractive exosome-miR-21-3p treatment relieved MCAO- or OGD-induced cerebral injury and inflammation through targeting TLR4.ConclusionThese results confirmed that MSC-derived exosome miR-542-3p prevented ischemia-induced glial cell inflammatory response via inhibiting TLR4. These results suggest possible therapeutic strategies for using exosome delivery of miR-542-3p to cure cerebral ischemic injury.
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页数:12
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