中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (6): 1360-1366.doi: 10.4103/1673-5374.386399

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

上调circ0000381可减轻脊髓损伤后小胶质细胞/巨噬细胞焦亡 

  

  • 出版日期:2024-06-15 发布日期:2023-11-18
  • 基金资助:
    国家自然科学基金项目(81901241)

Upregulation of circ0000381 attenuates microglial/macrophage pyroptosis after spinal cord injury

Yan Zhang1, #, Wenkai Zhang2, 3, #, Tao Liu2, Ziqian Ma2, Wenxiu Zhang1, Yun Guan4, 5, Xueming Chen1, 2, *   

  1. 1Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing, China; 2Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing, China; 3Department of Emergency Medicine, Aerospace Center Hospital, Beijing, China; 4Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 5Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Online:2024-06-15 Published:2023-11-18
  • Contact: Xueming Chen, MD, chenxueming@ccmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81901241 (to YZ).

摘要:

神经炎症会加剧脊髓损伤后的继发性损伤,而小胶质细胞/巨噬细胞焦亡对神经炎症十分重要。环状RNA也被证明可参与中枢神经系统疾病。但是环状RNA在脊髓损伤后调节小胶质细胞/巨噬细胞焦亡的功能作用和机制仍缺乏深入的研究。实验发现,在脊髓损伤雌性大鼠模型中,小胶质细胞/巨噬细胞发生焦亡,而脊髓中circ0000381水平上调。进一步的研究表明,circ0000381可作为内源性海绵,与miR-423-3p结合,并抑制后者的活性,并促进增加焦亡标志物NLRP3的表达。因此,circ0000381上调可能是限制脊髓损伤后小胶质细胞/巨噬细胞焦亡的代偿性变化。且敲低circ0000381能显著增强miR-423-3p对小胶质细胞/巨噬细胞焦亡的诱导。这项研究提示脊髓损伤后上调的circ0000381是减轻小胶质细胞/巨噬细胞焦亡的保护机制。因此,circ0000381可作为脊髓损伤治疗的新靶点。

https://orcid.org/0009-0001-8681-9660 (Xueming Chen)

关键词: 脊髓损伤, 小胶质细胞, 巨噬细胞, 焦亡, 神经炎症, 神经保护, circ0000381, miR-423-3p, 炎症小体, NLRP3, RNA测序

Abstract: Neuroinflammation exacerbates secondary damage after spinal cord injury, while microglia/macrophage pyroptosis is important to neuroinflammation. Circular RNAs (circRNAs) play a role in the central nervous system. However, the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied. In the present study, we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury, along with upregulated levels of circ0000381 in the spinal cord. Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p (miR-423-3p), which can increase the expression of NOD-like receptor 3 (NLRP3), a pyroptosis marker. Therefore, upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis. Indeed, knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis. Collectively, our findings provide novel evidence for the upregulation of circ0000381, which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord injury. Accordingly, circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.

Key words: circ0000381, inflammasome, macrophage, microglia, miR-423-3p, neuroinflammation, neuroprotection, NLRP3, pyroptosis, RNA-Seq, spinal cord injury