Department of Orthopedics, The first hospital of Changsha City, Changsha, 410005, China.
Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Neurochem Int. 2021 Feb;143:104929. doi: 10.1016/j.neuint.2020.104929. Epub 2020 Dec 23.
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.
在脊髓损伤 (SCI) 中，神经调节蛋白-1 (Nrg1) 迅速而持续地下调，对调节受损脊髓内星形胶质细胞的增殖和胶质瘢痕的形成有显著的积极作用。在这项研究中，我们揭示了 SCI 后长链非编码 RNA Ftx 和 Nrg1 的异常下调以及 miR-382-5p 的上调，这有助于小胶质细胞中的炎症反应，并影响 SCI 的修复。Ftx 的过表达显著减少，而 Ftx 的敲低进一步促进了 LPS 对炎症因子的影响，表明长链非编码 RNA Ftx 可能影响小胶质细胞的炎症反应。miR-382-5p 靶向 lncRNA Ftx 和 Nrg1，lncRNA Ftx 与 Nrg1 竞争 miR-382-5p 的结合，作为 ceRNA 发挥作用，从而抵消 miR-382-5p 介导的 Nrg1 抑制。miR-382-5p 的过表达显著增强，Nrg1 的过表达减弱了 LPS 对小胶质细胞内炎症因子的影响。在 LPS 刺激下，miR-382-5p 的过表达显著逆转了 Ftx 过表达的作用，而过表达 Nrg1 则显著逆转了 miR-382-5p 过表达的作用。总之，lncRNA Ftx/miR-382-5p/Nrg1 轴改善了小胶质细胞的炎症反应，可能促进 SCI 的修复。
