Medical Quality Management Department, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China.
Neurosurgery Department, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China.
J Neurogenet. 2023 Sep;37(3):103-114. doi: 10.1080/01677063.2023.2259995. Epub 2023 Oct 16.
Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve neural plasticity and promote neural function repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized and co-cultured with microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose deprivation/reoxygenation and LPS-induced microglia and converted microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced m6A methylation modification of nuclear factor erythroid 2-related factor 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the damage to neurons caused by microglia's inflammatory response. Finally, the changes in microglia polarization and neuron damage caused by FTO knockdown in NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial via transferring FTO, thereby resulting in neuroprotective effects.
缺血性脑卒中 (IS) 可导致神经元细胞丢失和功能缺陷。神经干细胞来源的外泌体 (NSC-Exos) 可改善 IS 后神经可塑性，并促进神经功能修复。然而，其潜在机制尚不清楚。在本研究中，我们对 NSC-Exos 进行了表征，并与小胶质细胞共培养。结果发现，NSC-Exos 可增加氧葡萄糖剥夺/复氧和 LPS 诱导的小胶质细胞中 NRF2 的表达，并将小胶质细胞从 M1 促炎表型转化为 M2 抗炎表型。NSC-Exos 通过肥胖相关基因 (FTO) 降低核因子红细胞 2 相关因子 2 (NRF2) mRNA 的 m6A 甲基化修饰。此外，NSC-Exos 可减轻小胶质细胞炎症反应引起的神经元损伤。最后，通过小胶质细胞中 NRF2 的过表达，可减轻 FTO 在 NSE-Exos 中的敲低对小胶质细胞极化和神经元损伤的改变。这些发现表明，NSC-Exos 通过转导 FTO 促进小胶质细胞中 NRF2 的表达和 M2 极化，从而发挥神经保护作用。
