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骨髓间充质干细胞衍生的外泌体 microRNA-124-3p 通过抑制新生大鼠中肿瘤坏死因子受体相关因子 6 减轻缺氧缺血性脑损伤。

Bone marrow mesenchymal stem cells-derived exosomal microRNA-124-3p attenuates hypoxic-ischemic brain damage through depressing tumor necrosis factor receptor associated factor 6 in newborn rats.

机构信息

Changhai Stroke Center, Changhai Hospital, Second Military Medical University, Shanghai China.

出版信息

Bioengineered. 2022 Feb;13(2):3194-3206. doi: 10.1080/21655979.2021.2016094.

Abstract

Mesenchymal stem cells (MSCs)-derived exosomes (Exo) are beneficial in the use of brain damages. Restrictively, the mechanism of Exo expressing miR-124-3p in hypoxic-ischemic brain damage (HIBD) is not completely comprehended. Thereupon, this work was put forward to reveal the action of bone marrow MSCs-derived Exo (BMSCs-Exo) expressing miR-124-3p in the illness. BMSCs were isolated and transfected with miR-124-3p agomir. Then, BMSCs-Exo were extracted and identified. The newborn HIBD rats were injected with miR-124-3p-modified BMSCs-Exo or tumor necrosis factor receptor associated factor 6 (TRAF6)-related vectors. Next, neurological functions, neuron pathological and structural damages, oxidative stress and neuronal apoptosis were observed. miR-124-3p and TRAF6 expression was tested, along with their targeting relationship. miR-124-3p was down-regulated, and TRAF6 was up-regulated in newborn HIBD rats. miR-124-3p targeted TRAF6. BMSCs-Exo improved neurological functions, alleviated neuron pathological and structural damages, suppressed oxidative stress and reduced neuronal apoptosis in newborn HIBD rats, whereas BMSCs-Exo-mediated effects were enhanced by restoring miR-124-3p. Silencing TRAF6 attenuated HIBD in newborn rats, but overexpression of TRAF6 reversed the protective role of miR-124-3p-overexpressing BMSCs-Exo. This work makes it comprehensive that up-regulated exosomal miR-124-3p ameliorates HIBD in newborn rats by targeting TRAF6, which replenishes the potential agents for curing HIBD.

摘要

间充质干细胞(MSCs)衍生的外泌体(Exo)在脑损伤的应用中是有益的。然而,外泌体表达 miR-124-3p 在缺氧缺血性脑损伤(HIBD)中的机制尚不完全清楚。因此,本研究旨在揭示骨髓间充质干细胞衍生的外泌体(BMSCs-Exo)表达 miR-124-3p 在该疾病中的作用。分离并转染 miR-124-3p 激动剂的 BMSCs,然后提取并鉴定 BMSCs-Exo。将新生 HIBD 大鼠注射 miR-124-3p 修饰的 BMSCs-Exo 或肿瘤坏死因子受体相关因子 6(TRAF6)相关载体。观察神经功能、神经元病理和结构损伤、氧化应激和神经元凋亡。检测 miR-124-3p 和 TRAF6 的表达及其靶向关系。新生 HIBD 大鼠中 miR-124-3p 下调,TRAF6 上调。miR-124-3p 靶向 TRAF6。BMSCs-Exo 改善新生 HIBD 大鼠的神经功能,减轻神经元病理和结构损伤,抑制氧化应激和减少神经元凋亡,而恢复 miR-124-3p 增强了 BMSCs-Exo 的介导作用。沉默 TRAF6 减轻新生大鼠的 HIBD,但过表达 TRAF6 逆转了 miR-124-3p 过表达的 BMSCs-Exo 的保护作用。本研究全面证实,上调的外泌体 miR-124-3p 通过靶向 TRAF6 改善新生大鼠的 HIBD,为治疗 HIBD 提供了潜在的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b011/8973938/c158388158fa/KBIE_A_2016094_UF0001_OC.jpg

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