Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 18, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12951-020-00630-5
Keywords
Autophagy; Bone marrow-derived macrophage; mTOR; Spinal cord injury; Small extracellular vesicle
Funding
- Natural Science Foundation of Jiangsu [BK20181490]
- National Natural Science Foundation of China [81772352, 81974335]
- Six Talent Peaks Project in Jiangsu Province [TD-SWYY-010]
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Background Spinal cord injury (SCI) has a very disabling central nervous system impact but currently lacks effective treatment. Bone marrow-derived macrophages (BMDMs) are recruited to the injured area after SCI and participate in the regulation of functional recovery with microglia. Previous studies have shown that M2 microglia-derived small extracellular vesicles (SEVs) have neuroprotective effects, but the effects of M2 BMDM-derived sEVs (M2 BMDM-sEVs) have not been reported in SCI treatment. Results In this study, we investigated the role of M2 BMDM-sEVs in vivo and in vitro for SCI treatment and its mechanism. Our results indicated that M2 BMDM-sEVs promoted functional recovery after SCI and reduced neuronal apoptosis in mice. In addition, M2 BMDM-sEVs targeted mammalian target of rapamycin (mTOR) to enhance the autophagy level of neurons and reduce apoptosis. MicroRNA-421-3P (miR-421-3p) can bind to the 3 ' untranslated region (3 ' UTR) of mTOR. MiR-421-3p mimics significantly reduced the activity of luciferase-mTOR 3 ' UTR constructs and increased autophagy. At the same time, tail vein injection of inhibitors of SEVs (Inh-sEVs), which were prepared by treatment with an miR-421-3p inhibitor, showed diminished protective autophagy of neuronal cells in vivo. Conclusions In conclusion, M2 BMDM-sEVs inhibited the mTOR autophagy pathway by transmitting miR-421-3p, which reduced neuronal apoptosis and promoted functional recovery after SCI, suggesting that M2 BMDM-sEVs may be a potential therapy for SCI.
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