Han Jun, Yang Si, Hao Xiaosheng, Zhang Bo, Zhang Hongbo, Xin Cuijuan, Hao Yunpeng
Department of Neonatology, The First Hospital of Jilin University, Changchun, China.
Department of Neurology, The First Hospital of Jilin University, Changchun, China.
Front Cell Dev Biol. 2021 Jan 11;8:579236. doi: 10.3389/fcell.2020.579236. eCollection 2020.
Hypoxia-ischemia brain damage (HIBD) is a neurological disorder occring in neonates, which is exacerbated by neuronal apoptosis. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for treating or preventing ischemia-related diseases. However, their mechanisms in HIBD remain unclear. Thus, we aimed to address the role of EV-derived microRNA (miR)-410 in HIBD. Neonatal HIBD mouse model was constructed using HI insult, from which neurons were isolated, followed by exposure to oxygen glucose deprivation (OGD). EVs were isolated from human umbilical cord (hUC)-derived MSCs. analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410, , , and . The functional roles of EV-derived miR-410 were determined using loss- and gain-of functions experiments, and by evaluating neuronal viability, cell-cycle distribution and neuronal apoptosis as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume . hUC-MSCs-derived EVs protected against HIBD and inhibited the OGD-induced neuronal apoptosis . miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted , which inversely mediated the expression of . Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing expression through downregulating expression . In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of downregulation, thereby providing a potential strategy for treating or preventing HIBD.
缺氧缺血性脑损伤（HIBD）是一种发生于新生儿的神经障碍性疾病，神经元凋亡会使其病情加重。间充质干细胞（MSCs）衍生的细胞外囊泡（EVs）已被认为是治疗或预防缺血相关疾病的一种有前景的策略。然而，它们在HIBD中的作用机制仍不清楚。因此，我们旨在探讨EV衍生的微小RNA（miR）-410在HIBD中的作用。采用缺氧缺血性损伤构建新生HIBD小鼠模型，从中分离神经元，然后使其暴露于氧糖剥夺（OGD）环境。从人脐带（hUC）衍生的MSCs中分离出EVs。采用分析、双荧光素酶报告基因和染色质免疫沉淀试验来确定miR-410、 、 和 之间的关系。通过功能缺失和功能获得实验，并通过评估神经元活力、细胞周期分布和神经元凋亡以及改良神经功能缺损评分（mNSS）、水肿形成和脑梗死体积，来确定EV衍生的miR-410的功能作用。hUC-MSCs衍生的EVs对HIBD具有保护作用，并抑制OGD诱导的神经元凋亡。miR-410通过hUC-MSCs-EVs成功递送至神经元，并负向靶向 ，其反过来介导 的表达。EV衍生的miR-410的上调促进了神经元的活力，但抑制了神经元的凋亡， 过表达可逆转这种作用。EV衍生的miR-410升高通过下调 表达来增加 表达，从而降低mNSS、水肿形成和脑梗死体积。总之，EV衍生的miR-410通过上调 下调的表达来抑制神经元凋亡，从而为治疗或预防HIBD提供了一种潜在策略。
