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Fan, Jingyi; Han, Yusen; Sun, Huanhuan; Sun, Shichao; Wang, Ying; Guo, Ruoyi; Guo, Jiangyuan; Tian, Xinyi; Wang, Jinli; Wang, Jueqiong
Biomedicine & pharmacotherapy, June 2023, 2023-Jun, 2023-06-00, 20230601, 2023-06-01, Letnik: 162Journal Article
Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disorder of the central nervous system. Accumulating evidence has underscored the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exos) containing bioactive compounds in MS. Herein, the current study sought to characterize the mechanism of BMSC-Exos harboring miR-367–3p both in BV2 microglia by Erastin-induced ferroptosis and in experimental autoimmune encephalomyelitis (EAE), a typical animal model of MS. Exosomes were firstly isolated from BMSCs and identified for further use. BV2 microglia were co-cultured with miR-367–3p-containing BMSC-Exos, followed by an assessment of cell ferroptosis. Mechanistic exploration was furthered by the interaction of miR-367–3p and its downstream regulators. Lastly, BMSC-Exos harboring miR-367–3p were injected into EAE mice for in vivo validation. BMSC-Exos carrying miR-367–3p restrained microglial ferroptosis in vitro. Mechanistically, miR-367–3p could bind to Enhancer of zeste homolog 2 (EZH2) and restrain EZH2 expression, leading to the over-expression of solute carrier family 7 member 11 (SLC7A11). Meanwhile, over-expression of SLC7A11 resulted in Glutathione Peroxidase 4 (GPX4) activation and ferroptosis suppression. Ectopic expression of EZH2 in vitro negated the protective effects of BMSC-Exos. Furthermore, BMSC-Exos containing miR-367–3p relieved the severity of EAE by suppressing ferroptosis and restraining EZH2 expression in vivo. Collectively, our findings suggest that BMSC-Exos carrying miR-367–3p brings about a significant decline in microglia ferroptosis by repressing EZH2 and alleviating the severity of EAE in vivo, suggesting a possible role of miR-367–3p overexpression in the treatment strategy of EAE. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. •Mesenchymal stem cell-derived exosomes (BMSC-Exos) suppress microglial ferroptosis•BMSC-Exos carrying miR-367–3p inhibit microglial ferroptosis via EZH2/SLC7A11 axis.•BMSC-Exos carrying miR-367–3p alleviate the severity of experimental autoimmune encephalomyelitis.•The role of BMSC-Exos carrying miR-367–3p in experimental autoimmune encephalomyelitis may be through the regulation of EZH2/SLC7A11-mediated ferroptosis.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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