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

• Published in: Life sciences (1973) Vol. 260; pp. 118403 - 9
• Main Authors: Zhao, Yangmin, Gan, Yunxiao, Xu, Gewei, Hua, Kouzhen, Liu, Dandan
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.11.2020; Elsevier BV
• Subjects: Cerebral blood flow; Cerebral infarction; Cerebral ischemia; cortex; Cysteinyl leukotriene receptor 2 (CysLT2R); Cytokines; Deprivation; Exosomes; Flow cytometry; Gene expression; glucose; hippocampus; In vivo methods and tests; infarction; Inflammation; Inflammatory response; Ischemia; Leukotrienes; Mesenchymal stem cell-derived exosomes (MSC-exos); Microglia; Microglial M1 polarization; MicroRNA-223; miRNA; neuroglia; Neurological diseases; Occlusion; oxygen; Polarization; protein synthesis; Proteins; Reperfusion; reperfusion injury; Ribonucleic acid; RNA; secretion; Surgery; therapeutics; Western blotting; Cerebral ischemia; Mesenchymal stem cell-derived exosomes (MSC-exos); Microglial M1 polarization; Cysteinyl leukotriene receptor 2 (CysLT2R); MicroRNA-223
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2020.118403

To explore the therapeutic effect and possible mechanism of exosomes from MSCs overexpressing miR-223 on cerebral ischemia and microglia polarization mediated inflammation. 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 (CysLT2R) in vivo and in vitro. 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 NMLTC4 with a concentration-dependent manner. Western blot and qRT-PCR also revealed exosomal miR-223-3p decreased mRNA and protein expression of CysLT2R in vitro and in vivo. Exosomal miR-223-3p from MSCs attenuated cerebral ischemia/reperfusion injury through inhibiting microglial M1 polarization mediated pro-inflammatory response, which may be related with inhibitory effect of exosomal miR-223-3p on CysLT2R. •Exosomal miR-223-3p improved neurological deficit, learning and memory abilities after cerebral ischemia.•Exosomal miR-223-3p suppressed microglia M1 polarization and promoted M2 activation.•Exosomal miR-223-3p increased anti-inflammatory factors secretion and decreased pro-inflammatory cytokines production.•Exosomal miR-223-3p inhibited CysLT2R mRNA expression and protein production.