Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization
Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization
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DOI：
10.1159/000490078and
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Li, Longxuan
中科院分区：
文献类型：
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作者：
Jiang, Mei;Wang, Hairong;Li, Longxuan
背景/目标：最近的研究表明，脂肪干细胞（ADSCs）分泌的外泌体在缺血性损伤的治疗中具有重要作用。然而，治疗机制尚不清楚。本研究旨在研究富含microRNA（miR）-30 d-Sp的ADSC来源的exosomes是否对急性缺血性卒中（AIS）具有保护作用。方法：在本研究中，对70例AIS患者和35例健康对照者的炎症因子和miR-30 d-5 p表达进行了评估。外泌体通过透射电子显微镜表征，并使用纳米颗粒跟踪分析进一步检查。建立AIS大鼠模型和缺氧缺糖（OGD）原代小胶质细胞体外模型，以研究来自miR-30 d-5 p过表达的ADSC的外泌体在缺血诱导的神经损伤中的保护机制。结果如下：结果显示，AIS后，患者和动物模型中炎性细胞因子的表达增加，而炎性细胞因子IL-4、IL-10和miR-30 d-Sp的表达减少。此外，体外研究表明，抑制自噬显著降低了OGD诱导的炎症反应。此外，外泌体治疗通过逆转OGD诱导的和自噬介导的小胶质细胞极化为Ml而更有效地抑制炎症反应。此外，体内研究表明，来源于ADSC的外泌体通过抑制自噬和促进M2小胶质细胞/巨噬细胞极化显著减少梗死的脑损伤面积。结论：我们的研究结果表明，miR-30 d-5 p增强的ADSC衍生的外泌体通过抑制自噬介导的小胶质细胞极化至M1来预防脑损伤。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-Sp have a protective effect on acute ischemic stroke (AIS). Methods: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia -induced nerve injury. Results: The results showed that following AIS, the expression of inflammatory cytokines increased, while the antiinflammatory cytokines IL-4, IL-10, and miR-30d-Sp decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to Ml. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. Conclusions: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1. (C) 2018 The Author(s) Published by S. Karger AG, Basel