Chang Andrew, Dias Abeyagunawardene Shevanka, Zheng Xiaohang, Jin Haiming, Wang Qingqing, Xu Jiake
Medical School, The University of Western Australia, Perth, WA 6009, Australia.
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Genes (Basel). 2025 Apr 28;16(5):514. doi: 10.3390/genes16050514.
Spinal cord injury (SCI) remains a profound medical challenge, with limited therapeutic options available. Studies focusing on individual molecular markers have limitations in addressing the complex disease process.
This study utilizes RNA-sequencing (RNA-seq) to investigate the differentially expressed genes (DEGs) in spinal cord tissue from a rat SCI model at 1 and 21 days post-injury (dpi). After data processing and analysis, a series of biological pathway enrichment analyses were performed using online tools DAVID and GSEA. Interactions among the enriched genes were studied using Cytoscape software to visualize protein-protein interaction networks.
Our analysis identified 595 DEGs, with 399 genes significantly upregulated and 196 significantly downregulated at both time points. was the most upregulated gene at 21 dpi, with a significant fold change at 1 dpi. Conversely, was the most downregulated gene. Key immune response processes, including tumor necrosis factor (TNF) production, phagocytosis, and complement cascades, as well as systemic lupus erythematosus (SLE)-associated pathways, were enriched in the upregulated group. The enriched pathways in the downregulated group were related to the myelin sheath and neuronal synapse. Genes of interest from the most significantly downregulated DEGs were , , , , and . Upregulation of Fc-γ receptor genes, including and , points to potential autoimmune mechanisms.
Our findings highlight complex immune and autoimmune responses that contribute to ongoing inflammation and tissue damage post-SCI, underscoring new avenues for therapeutic interventions targeting these molecular processes.
脊髓损伤（SCI）仍然是一项严峻的医学挑战，可用的治疗选择有限。专注于单个分子标记的研究在应对复杂的疾病过程方面存在局限性。
本研究利用RNA测序（RNA-seq）来研究大鼠脊髓损伤模型在损伤后1天和21天脊髓组织中差异表达基因（DEG）。经过数据处理和分析后，使用在线工具DAVID和GSEA进行了一系列生物途径富集分析。使用Cytoscape软件研究富集基因之间的相互作用，以可视化蛋白质-蛋白质相互作用网络。
我们的分析确定了595个DEG，在两个时间点均有399个基因显著上调，196个显著下调。 是损伤后21天上调最明显的基因，在损伤后1天有显著的倍数变化。相反， 是下调最明显的基因。上调组中富集了关键免疫反应过程，包括肿瘤坏死因子（TNF）产生、吞噬作用和补体级联反应，以及与系统性红斑狼疮（SLE）相关的途径。下调组中富集的途径与髓鞘和神经元突触有关。下调最显著的DEG中感兴趣的基因有 、 、 、 和 。Fc-γ受体基因（包括 和 ）的上调表明存在潜在的自身免疫机制。
我们的研究结果突出了导致SCI后持续炎症和组织损伤的复杂免疫和自身免疫反应，强调了针对这些分子过程的治疗干预新途径。
