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The lncRNA Ftx/miR-382-5p/Nrg1 axis improves the inflammation response of microglia and spinal cord injury repair
Neurochemistry international ( IF 4.2 ) Pub Date : 2020-12-23 , DOI: 10.1016/j.neuint.2020.104929
Weineng Xiang 1 , Lin Jiang 1 , Yun Zhou 1 , Zhiyue Li 2 , Qun Zhao 2 , Tianding Wu 3 , Yong Cao 3 , Jiahui Zhou 2
Affiliation  

During spinal cord injury (SCI), a quick and sustained decline of Neuregulin-1 (Nrg1) has been observed, exerting a significant positive effect in modulating the proliferation of astrocytes and the formation of glial scars within the damaged spinal cord. In this study, we revealed the abnormal downregulation of lncRNA Ftx and Nrg1 and upregulation of miR-382-5p after SCI, which contributed to the inflammatory response in microglial cells and affected SCI repair. Ftx overexpression was significantly reduced, and Ftx knockdown further promoted LPS effects on the inflammatory factors, indicating that lncRNA Ftx might affect the microglial inflammatory response. miR-382-5p targeted both lncRNA Ftx and Nrg1, and lncRNA Ftx competed with Nrg1 for miR-382-5p binding to act as a ceRNA, therefore counteracting miR-382-5p-mediated inhibition of Nrg1. miR-382-5p overexpression was significantly enhanced, and Nrg1 overexpression attenuated LPS effects on inflammatory factors within the microglia. Under LPS stimulation, the effects of Ftx overexpression were significantly reversed by overexpression of miR-382-5p, and the effects of miR-382-5p overexpression were significantly reversed by Nrg1 overexpression. In summary, the lncRNA Ftx/miR-382-5p/Nrg1 axis improves the inflammation response of the microglia, which might improve SCI repair.



中文翻译:

lncRNA Ftx/miR-382-5p/Nrg1轴改善小胶质细胞炎症反应和脊髓损伤修复

在脊髓损伤 (SCI) 期间,已观察到 Neuregulin-1 (Nrg1) 的快速持续下降,在调节星形胶质细胞增殖和受损脊髓内胶质瘢痕形成方面发挥显着的积极作用。在这项研究中,我们揭示了 SCI 后 lncRNA Ftx 和 Nrg1 的异常下调和 miR-382-5p 的上调,这有助于小胶质细胞的炎症反应并影响 SCI 修复。Ftx 过表达显着降低,Ftx 敲低进一步促进 LPS 对炎症因子的影响,表明 lncRNA Ftx 可能影响小胶质细胞炎症反应。miR-382-5p 同时靶向 lncRNA Ftx 和 Nrg1,并且 lncRNA Ftx 与 Nrg1 竞争 miR-382-5p 结合以充当 ceRNA,因此抵消了 miR-382-5p 介导的 Nrg1 抑制。miR-382-5p 过表达显着增强,Nrg1 过表达减弱 LPS 对小胶质细胞内炎症因子的影响。在LPS刺激下,过表达miR-382-5p显着逆转Ftx过表达的影响,过表达Nrg1显着逆转miR-382-5p过表达的影响。总之,lncRNA Ftx/miR-382-5p/Nrg1 轴改善了小胶质细胞的炎症反应,这可能会改善 SCI 修复。

更新日期:2020-12-25
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