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

被引：17

作者：

Jiang, Mei ^{[1
]}

Wang, Hairong ^{[2
]}

Zin, Mingming ^{[3
]}

Yang, Xuelian ^{[1
]}

Ji, Haifeng ^{[1
]}

Jiang, Yufeng ^{[4
]}

Zhang, Hanwen ^{[1
]}

Wu, Feifei ^{[1
]}

Wu, Guolu ^{[1
]}

Lai, Xiaoyin ^{[1
]}

Cai, Liying ^{[1
]}

Hu, Rongguo ^{[1
]}

Xu, Limin ^{[3
]}

Li, Longxuan ^{[1
]}

机构：

[1] Second Mil Med Univ, Shanghai Gongli Hosp, Dept Neurol, 219 Miao Pu Rd, Shanghai 200135, Peoples R China

[2] Second Mil Med Univ, Shanghai Gongli Hosp, Dept Cardiol, Shanghai, Peoples R China

[3] Second Mil Med Univ, Shanghai Gongli Hosp, Dept Cent Lab, Shanghai, Peoples R China

[4] Anhui Med Univ, Dept Clin Med, Clin Med Sch, Hefei, Anhui, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2018年 / 47卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Acute ischemic stroke; MiR-30d-5p; Microglial/macrophage polarization; Autophagy; Exosome; MESENCHYMAL STROMAL CELLS; TRANSIENT FOCAL ISCHEMIA; MACROPHAGE POLARIZATION; INFLAMMATORY RESPONSE; PATHWAYS; DELIVERY; PLAYS; LIVER; M1; ACTIVATION;

D O I：

10.1159/000490078and

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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

引用

页码：864 / 878

页数：15