Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

作者：Mei Jiang, Hairong Wang, Mingming Jin, Xuelian Yang, Hai‐Feng Ji, Yufeng Jiang, Hanwen Zhang, Feifei Wu, Guolu Wu, Xiaoyin Lai, Liying Cai, Rongguo Hu, Limin Xu, Longxuan Li · 发表于：Cellular Physiology and Biochemistry · 年份：2018 · DOI：10.1159/000490078 · 被引用次数：310 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Extracellular vesicles in disease、MicroRNA in disease regulation

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-5p 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 anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p 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 M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area o...