Fang Yuming, Chen Weican, Zhang Yan, Yang Yushen, Wang Shengnan, Pei Mengqin, Zhou Yilin, Lin Shu, He Hefan
Department of Anaesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
Department of Anesthesiology, Zhuzhou Central Hospital, Zhuzhou, Hunan Province, China.
Neural Regen Res. 2025 Apr 29. doi: 10.4103/NRR.NRR-D-24-01451.
Spinal cord injury (SCI) is a critical event characterized by intricate pathogenic mechanisms. Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues, their role in SCI has yet to be determined. In this study, we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following SCI. We found morphological, concentration, and functional differences between exosomes extracted from injured and normal spinal cord tissues, and identified proinflammatory effects associated with SCI-generated tissue exosomes (SCI-Exos) but not with exosomes derived from normal spinal cord tissue (Sham-Exos). Our in vivo and in vitro analyses showed that SCI-Exos promoted microglial M1 polarization and inflammatory cytokine expression, thereby exacerbating tissue and neuronal injury in the spinal cord. In addition, the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in SCI-Exos than in Sham-Exos. We further found that SCI-Exos-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factorkappa B pathway, thereby promoting microglial M1 polarization and inflammatory cytokine expression. These findings suggest that injury-induced miR-155-5pcontaining exosomes exacerbate SCI via the promotion of microglial M1 polarization and inflammatory responses. Thus, targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-SCI.
脊髓损伤（SCI）是一种具有复杂致病机制的关键事件。尽管最近的研究强调组织外泌体是不同器官和组织中炎症反应的关键介质，但其在脊髓损伤中的作用尚未确定。在本研究中，我们调查了脊髓组织外泌体在脊髓损伤后炎症反应中的作用和机制。我们发现从损伤和正常脊髓组织中提取的外泌体在形态、浓度和功能上存在差异，并确定了与脊髓损伤产生的组织外泌体（SCI-Exos）相关的促炎作用，而与正常脊髓组织来源的外泌体（假手术组外泌体，Sham-Exos）无关。我们的体内和体外分析表明，SCI-Exos促进了小胶质细胞的M1极化和炎性细胞因子表达，从而加剧了脊髓中的组织和神经元损伤。此外，外泌体miRNA测序与实验验证相结合表明，SCI-Exos中的miR-155-5p水平高于Sham-Exos。我们进一步发现，SCI-Exos来源的miR-155-5p显著抑制叉头框O3a磷酸化并激活核因子κB通路，从而促进小胶质细胞的M1极化和炎性细胞因子表达。这些发现表明，损伤诱导的含miR-155-5p的外泌体通过促进小胶质细胞的M1极化和炎症反应而加剧脊髓损伤。因此，靶向miR-155-5p表达或外泌体分泌可能是减轻脊髓损伤后炎症和减少继发性损伤的新策略。
