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Excess administration of miR-340-5p ameliorates spinal cord injury-induced neuroinflammation and apoptosis by modulating the P38-MAPK signaling pathway
Brain, Behavior, and Immunity ( IF 15.1 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.bbi.2020.01.025
Zhanyang Qian 1 , Jie Chang 1 , Fan Jiang 1 , Dawei Ge 2 , Lei Yang 2 , You Li 1 , Hongtao Chen 1 , Xiaojian Cao 1
Affiliation  

Spinal cord injury (SCI) is a destructive polyneuropathy that can result in loss of sensorimotor function and sphincter dysfunction, and even death in critical situations. MicroRNAs (miRs) are a series of non-coding RNA molecules that are involved in transcriptional regulation. Previous studies have demonstrated that modulation of multiple miRs is involved in neurological recovery after SCI. However, the functions of miR-340-5p in SCI remain uncertain. Therefore, we probed the therapeutic effect and mechanism of miR-340-5p in microglia in vitro and in vivo in SCI rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were employed to examine the alterations in miR-340-5p and P38 levels in SCI rats. miR-340-5p targets in microglia were ascertained using luciferase reporter assays, immunofluorescence analyses, and western blotting. We also established an SCI model and administered miR-340-5p. The effects of miR-340-5p on the amelioration of inflammation, oxidative stress, and apoptosis following SCI were assessed using immunofluorescence, immunohistochemistry, and histological analyses. Finally, locomotor function recovery was determined using the Basso, Beattie, Bresnahan rating scale. In our study, the expression profiles and luciferase assay results clarified that P38 was a target of miR-340-5p, which was associated with activation of the P38-MAPK signaling pathway. Elevation of miR-340-5p decreased P38 expression, subsequently inhibiting the inflammatory reaction. SCI-induced secondary neuroinflammation was relieved under miR-340-5p treatment. Moreover, by controlling neuroinflammation, the increased levels of miR-340-5p might counter oxidative stress and reduce the degree of apoptosis. We also observed decreasing gliosis and glial scar formation and increasing neurotrophin expression at the chronic stage of SCI. Together, these potential effects of miR-340-5p treatment ultimately improved locomotor function recovery in SCI rats.

中文翻译:

过量施用 miR-340-5p 通过调节 P38-MAPK 信号通路改善脊髓损伤诱导的神经炎症和细胞凋亡

脊髓损伤 (SCI) 是一种破坏性多发性神经病,可导致感觉运动功能丧失和括约肌功能障碍,甚至在危急情况下死亡。MicroRNAs (miRs) 是一系列参与转录调控的非编码 RNA 分子。先前的研究表明,多个 miR 的调节参与了 SCI 后的神经功能恢复。然而,miR-340-5p 在 SCI 中的功能仍不确定。因此,我们在SCI大鼠体外和体内探讨了miR-340-5p在小胶质细胞中的治疗效果和机制。采用逆转录-定量聚合酶链反应 (RT-qPCR) 和蛋白质印迹法检测 SCI 大鼠 miR-340-5p 和 P38 水平的变化。使用荧光素酶报告基因检测确定小胶质细胞中的 miR-340-5p 靶标,免疫荧光分析和蛋白质印迹。我们还建立了 SCI 模型并管理了 miR-340-5p。使用免疫荧光、免疫组织化学和组织学分析评估 miR-340-5p 对 SCI 后炎症、氧化应激和细胞凋亡的改善的影响。最后,使用 Basso、Beattie、Bresnahan 评定量表确定运动功能恢复。在我们的研究中,表达谱和荧光素酶测定结果阐明 P38 是 miR-340-5p 的靶标,这与 P38-MAPK 信号通路的激活有关。miR-340-5p 的升高降低了 P38 的表达,随后抑制了炎症反应。在 miR-340-5p 治疗下,SCI 诱导的继发性神经炎症得到缓解。此外,通过控制神经炎症,miR-340-5p 水平的增加可能会对抗氧化应激并降低细胞凋亡的程度。我们还观察到在 SCI 的慢性阶段神经胶质增生和胶质瘢痕形成减少以及神经营养因子表达增加。总之,miR-340-5p 治疗的这些潜在作用最终改善了 SCI 大鼠的运动功能恢复。
更新日期:2020-07-01
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