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Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia through inhibiting microglial M1 polarization mediated inflammation

Zhao, Yangmin, Gan, Yunxiao, Xu, Gewei, Hua, Kouzhen, Liu, Dandan·2020·Life Sciences
DOI 10.1016/j.lfs.2020.118403
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Abstract

Aims To explore the therapeutic effect and possible mechanism of exosomes from MSCs overexpressing miR-223 on cerebral ischemia and microglia polarization mediated inflammation. Main methods Rats after middle cerebral artery occlusion and reperfusion (MCAO/R) surgery and microglia BV-2 exposed to oxygen and glucose deprivation (OGD) and cysteinyl leukotrienes (CysLTs) stimulation were subject to exosomes from miR-223-3p transfected MSCs treatment, respectively. Behavioral tests were applied to assess the rats' neurological function. FACS was used to analyze M1/M2 microglia BV-2. production of cytokines in the ischemic hemisphere and BV-2 was detected by ELISA or qRT-PCR. Western blotting and qRT-PCR were also used to examine the expression of cysteinyl leukotriene receptor 2 (CysLT 2 R) in vivo and in vitro. Key findings Exosomes from MSCs over expressing miR-223-3p decreased MCAO/R induced cerebral infarct volume, improved neurological deficits, promoted learning and memorizing abilities. They suppressed pro-inflammatory factors expression and promoted anti-inflammatory factors secretion in the ischemic cortex and hippocampus. In vitro, exosomal miR-223-3p exhibited a more evident impact on modulating mRNA expression and protein production of cytokines. It promoted M2 microglia transformation of M1 microglia induced by NMLTC 4 with a concentration-dependent manner. Western blot and qRT-PCR also revealed exosomal miR-223-3p decreased mRNA and protein expression of CysLT 2 R i…

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Metadata

Authors
Zhao, Y., Gan, Y., Xu, G., Hua, K., & Liu, D.
Venue
Life Sciences
Publisher
Elsevier BV
Published
2020-11
Volume
260
Pages
118403
ISSN
0024-3205
DOI
10.1016/j.lfs.2020.118403
Cited by
134
References
2
Language
en
Licence
Funders
Natural Science Foundation (LY18H090011, LGF20H110001)

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Zhao, Y., Gan, Y., Xu, G., Hua, K., & Liu, D. (2020). Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia through inhibiting microglial M1 polarization mediated inflammation. Life Sciences. https://doi.org/10.1016/j.lfs.2020.118403