神经干细胞外泌体 miR-9a-5p 过表达改善缺血性中风大鼠存活率和神经发生的机制

IF 2.9 4区 医学 Q1 Medicine
Jiale Liu, Chaoqun Lin, Chenyang Gu, Qiankun Zhang, Tingle Feng, Wenjie Duan, Jiajun Huang, J. Long, Yunhui Qiu, Waqas Ahmed, Ahsan Ali Khan, Hengsen Cai, Yong Hu, Zhihan Zhu, Shiying Huang, Lukui Chen
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引用次数: 0

摘要

缺血性脑卒中是一种严重的疾病,可导致肢体残疾和死亡。本文研究了神经干细胞(NSCs)外泌体中上调的miRNA对大鼠缺血性中风的保护作用及其分子机制,以揭示外泌体的治疗靶点,并提出治疗缺血性中风的新方法。评估了miR-9a-5p上调对NSCs分化的影响。在体外和体内研究了从正常 NSCs 和 miR-9a-5p 上调的 NSCs 提取的外泌体对细胞存活、分化和 AMPK 激活的影响。高通量测序分析表明,miR-9a-5p 在不同分化阶段的 NSC 外泌体中有不同表达。外泌体中 MiR-9a-5p 的上调促进了 NSCs 的细胞分化。此外,它还能敏化 AMPK 信号通路。缺氧/葡萄糖再灌注后,NSCs 的分化得到恢复,外泌体显著减少了细胞凋亡。MiR-9a-5p 外泌体降低了缺血性脑卒中大鼠体内血脑屏障的通透性和梗死体积。神经细胞凋亡减少,这表明 miR-9a-5p 可抑制体内细胞凋亡。 miR-9a-5p外泌体诱导并增加了MACO/R大鼠的AMPK活化。miR-9a-5p外泌体可促进AMPK磷酸化,提高NSC存活率并促进细胞分化;这可通过维持足够数量的神经细胞和促进内源性NSC分化来抑制缺血性中风的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanism of Neural Stem Cell-Derived Exosomal miR-9a-5p Overexpression Improving Survival and Neurogenesis in Ischemic Stroke Rats
As a momentous condition disease, ischemic stroke could lead to physical disability and death. Here, the protective effect of miRNA up-regulated in neural stem cells (NSCs) derived exosomes on ischemic stroke in rats and their molecular mechanisms were investigated to reveal the therapeutic target of exosomes and suggests new approaches to treat ischemic stroke. miRNAs differentially expressed in exosomes derived from NSCs at various differentiation stages were detected by high-throughput sequencing for miRNAs. The impacts of miR-9a-5p upregulation were assessed on the differentiation of NSCs. The effects of exosomes derived from normal NSCs and NSCs with up-regulated miR-9a-5p on cell survival and differentiation and AMPK activation were investigated in vitro and in vivo. The high-throughput sequencing analysis revealed that miR-9a-5p was differentially expressed in NSC-derived exosomes at various stages of differentiation. MiR-9a-5p upregulation in exosomes promoted cell differentiation of NSCs. Furthermore, it can sensitized the AMPK signaling pathway. Following deprivation/reperfusion of oxygen-glucose, the differentiation of NSCs was restored, and exosomes significantly reduced cell apoptosis. MiR-9a-5p exosomes reduced the blood-brain barrier permeability and the infarct volume of rats with ischemic stroke in vivo. Neural cell apoptosis was reduced, thus indicating that miR-9a-5p could inhibit the cell apoptosis in vivo. AMPK activation was induced and increased in the MACO/R rat with miR-9a-5p exosomes. MiR-9a-5p exosomes could promote AMPK phosphorylation, increase NSC survival and enhance cell differentiation; this could inhibit the progression of ischemic stroke by maintaining an adequate number of neural cells and promoting endogenous NSC differentiation.
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来源期刊
CiteScore
4.30
自引率
17.20%
发文量
145
审稿时长
2.3 months
期刊介绍: Information not localized
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