The role of astrocyte-derived extracellular vesicles in cellular microenvironment remodeling after spinal cord injury: A study based on quantitative proteomics analysis

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-05-27 DOI:10.1016/j.expneurol.2025.115321

Zhenghuan Zhu , Yi Xu , Kejie Wang , Xu Xu , Yu Song , Baizhen Zhao , Wenge Ding , Jinbo Liu , Zhiwen Song

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引用次数: 0

Abstract

After spinal cord injury (SCI), astrocytes (AS), the most abundant glial cells in the central nervous system, closely interact with other nerve cells. The precise mechanism by which astrocytes remodel the cellular microenvironment (CME) remains unclear; however, the extracellular vesicles (EVs) they release may facilitate communication between cells by transporting biological macromolecules. This study aimed to elucidate the role of astrocyte-derived EVs in modulating CME after SCI. An in vitro model of reactive astrocytes (RA) was developed under simulated SCI conditions, followed by proteomic analysis of EVs isolated from RA and AS. Differential protein expression was assessed using quantitative proteomics, complemented by gene set enrichment analysis to elucidate the associated biological functions. Our results indicate that AS-EVs provide neuroprotective benefits by attenuating microglial activation, decreasing neuronal apoptosis, promoting axonal growth, and facilitating the maturation of oligodendrocyte precursor cells, thereby improving motor function recovery in murine models. Conversely, RA-EVs exhibited deleterious effects, exacerbating inflammation and impeding functional recovery. CC Motif Chemokine Ligand 7 (CCL7) was identified as a critical secretory protein mediating these adverse effects. These findings elucidate the neuroprotective and regenerative mechanisms mediated by astrocyte-derived EVs, highlighting the therapeutic potential of CCL7-targeted interventions in promoting recovery after SCI.

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星形胶质细胞来源的细胞外囊泡在脊髓损伤后细胞微环境重塑中的作用：基于定量蛋白质组学分析的研究

脊髓损伤后，星形胶质细胞是中枢神经系统中最丰富的胶质细胞，与其他神经细胞密切相互作用。星形胶质细胞重塑细胞微环境（CME）的确切机制尚不清楚；然而，它们释放的细胞外囊泡（EVs）可能通过运输生物大分子促进细胞间的通讯。本研究旨在阐明星形胶质细胞衍生的ev在脊髓损伤后CME调节中的作用。在模拟SCI条件下建立了体外反应性星形胶质细胞（RA）模型，并对RA和AS分离的ev进行了蛋白质组学分析。利用定量蛋白质组学评估差异蛋白表达，辅以基因集富集分析来阐明相关的生物学功能。我们的研究结果表明，as - ev通过减弱小胶质细胞激活，减少神经元凋亡，促进轴突生长，促进少突胶质前体细胞成熟，从而改善小鼠模型的运动功能恢复，从而具有神经保护作用。相反，ra - ev表现出有害作用，加剧炎症并阻碍功能恢复。CC Motif趋化因子配体7 （CCL7）被认为是介导这些不良反应的关键分泌蛋白。这些发现阐明了星形胶质细胞衍生的ev介导的神经保护和再生机制，突出了ccl7靶向干预在促进脊髓损伤后恢复方面的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.