Downregulation of Circular RNA Gla Reduced Astrocyte Inflammatory Status by Regulating miR-488/MEKK1 Levels and Promoted Functional Recovery After Spinal Cord Injury

环状 RNA Gla 的下调通过调节 miR-488/MEKK1 水平降低星形胶质细胞炎症状态并促进脊髓损伤后的功能恢复

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作者:Qiang Shao #, Ying Zhang #, Zhiyuan Zhang, Wei Jiang, Yongcheng Yin, Yuepeng Fang, Ce Zhang, Qingfa Chen, Bin Ning

Background

Post-spinal cord injury (SCI) inflammation correlates with neurologic recovery. Through sequencing, we explored the roles of a differentially expressed circRNA in mice after SCI, circGla, on inflammation and recovery of SCI.

Conclusion

Following SCI, downregulation of circGla expression in astrocytes can reduce inflammatory manifestations and stimulate long-term functional recovery in mice through miR-488 and MEKK1.

Methods

The T8-T10 SCI model was established in C57BL6 mice. HE staining and RT-qPCR verified circGla upregulation

Results

Following SCI, the circular RNA circGla levels increased and it existed in the astrocyte cytoplasm. circGla knockdown reduced inflammation and improved neurological recovery in vivo. The correlation between circGla and proinflammatory factors was confirmed in vitro. circGla bound to miR-488, and the high miR-488 level was associated with the low astrocyte inflammatory state. miR-488 bound to MEKK1 mRNA, and upregulation or knockdown of circGla or miR-488 affected MAPK pathway-related protein expression.

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