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M2 Microglia Extracellular Vesicle miR-124 Regulates Neural Stem Cell Differentiation in Ischemic Stroke via AAK1/NOTCH.
Song, Yaying; Shi, Rubing; Liu, Yingjun; Cui, Fengzhen; Han, Lu; Wang, Chuandong; Chen, Tingting; Li, Zongwei; Zhang, Zhijun; Tang, Yaohui; Yang, Guo-Yuan; Guan, Yangtai.
Afiliação
  • Song Y; Department of Neurology, Renji Hospital of Shanghai Jiao Tong University, China (Y.S., L.H., Y.G.).
  • Shi R; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China (R.S., F.C., T.C., Z.L., Z.Z., Y.T., G.-Y.Y.).
  • Liu Y; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, China (Y.L.).
  • Cui F; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China (R.S., F.C., T.C., Z.L., Z.Z., Y.T., G.-Y.Y.).
  • Han L; Department of Neurology, Renji Hospital of Shanghai Jiao Tong University, China (Y.S., L.H., Y.G.).
  • Wang C; Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China (C.W.).
  • Chen T; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China (R.S., F.C., T.C., Z.L., Z.Z., Y.T., G.-Y.Y.).
  • Li Z; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China (R.S., F.C., T.C., Z.L., Z.Z., Y.T., G.-Y.Y.).
  • Zhang Z; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China (R.S., F.C., T.C., Z.L., Z.Z., Y.T., G.-Y.Y.).
  • Tang Y; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China (R.S., F.C., T.C., Z.L., Z.Z., Y.T., G.-Y.Y.).
  • Yang GY; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, China (R.S., F.C., T.C., Z.L., Z.Z., Y.T., G.-Y.Y.).
  • Guan Y; Department of Neurology, Renji Hospital of Shanghai Jiao Tong University, China (Y.S., L.H., Y.G.).
Stroke ; 54(10): 2629-2639, 2023 10.
Article em En | MEDLINE | ID: mdl-37586072
ABSTRACT

BACKGROUND:

Small extracellular vesicles (sEVs) derived from M2 microglia (M2-microglia-derived small extracellular vesicles [M2-sEVs]) contribute to central nervous system repair, although the underlying mechanism remains unknown. In this study, we aimed to identify the mechanism through which microRNA-124 (miR-124) carried in sEVs promotes neural stem cell (NSC) proliferation and neuronal differentiation in the ischemic mouse brain.

METHODS:

M2-sEVs with or without miR-124 knockdown were injected intravenously for 7 consecutive days after transient middle cerebral artery occlusion surgery. The atrophy volume, neurological score, and degree of neurogenesis were examined at different time points after ischemic attack. NSCs treated with different sEVs were subjected to proteomic analysis. Target protein concentrations were quantified, and subsequent bioinformatic analysis was conducted to explore the key signaling pathways.

RESULTS:

M2-sEV transplantation promoted functional neurological recovery following transient middle cerebral artery occlusion injury. M2-sEV treatment decreased the brain atrophy volume, neurological score, and mortality rate. The effect was reserved by knockdown of miR-124 in M2-sEVs. M2-sEVs promoted proliferation and differentiation of mature neuronal NSCs in vivo. Proteomic analysis of NSC samples treated with M2-sEVs with and without miR-124 knockdown revealed that AAK1 (adaptor-associated protein kinase 1) was the key responding protein in NSCs. The binding of AAK1 to Notch promoted the differentiation of NSCs into neurons rather than astrocytes.

CONCLUSIONS:

Our data suggest that AAK1/Notch is the key pathway in NSCs that responds to the miR-124 carried within M2-sEVs in the ischemic brain. M2-sEVs carrying ample quantities of miR-124 promote functional recovery after ischemic stroke by enhancing NSC proliferation and differentiation. Targeting of M2-sEVs could represent a potential therapeutic strategy for brain recovery.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Células-Tronco Neurais / Vesículas Extracelulares / AVC Isquêmico Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Células-Tronco Neurais / Vesículas Extracelulares / AVC Isquêmico Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article