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与癫痫引起的免疫调节和炎症反应相关的关键蛋白编码基因与小胶质细胞有关。

Key protein-coding genes related to microglia in immune regulation and inflammatory response induced by epilepsy.

机构信息

Department of Pathophysiology, Chongqing Medical University, Chongqing 400010, China.

Institute of Neuroscience, Chongqing Medical University, Chongqing 400010, China.

出版信息

Math Biosci Eng. 2021 Nov 2;18(6):9563-9578. doi: 10.3934/mbe.2021469.

Abstract

Several studies have shown a link between immunity, inflammatory processes, and epilepsy. Active neuroinflammation and marked immune cell infiltration occur in epilepsy of diverse etiologies. Microglia, as the first line of defense in the central nervous system, are the main effectors of neuroinflammatory processes. Discovery of new biomarkers associated with microglia activation after epileptogenesis indicates that targeting specific molecules may help control seizures. In this research, we used a combination of several bioinformatics approaches, including RNA sequencing, to explore differentially expressed genes (DEGs) in epileptic lesions and control samples, and to construct a protein-protein interaction (PPI) network for DEGs, which was examined utilizing plug-ins in Cytoscape software. Finally, we aimed to identify 10 hub genes in immune and inflammation-related sub-networks, which were subsequently validated in real-time quantitative polymerase chain reaction analysis in a mouse model of kainic acid-induced epilepsy. The expression patterns of nine genes were consistent with sequencing outcomes. Meanwhile, several genes, including CX3CR1, CX3CL1, GPR183, FPR1, P2RY13, P2RY12 and LPAR5, were associated with microglial activation and migration, providing novel candidate targets for immunotherapy in epilepsy and laying the foundation for further research.

摘要

多项研究表明免疫、炎症过程和癫痫之间存在关联。在不同病因的癫痫中,存在活跃的神经炎症和明显的免疫细胞浸润。小胶质细胞作为中枢神经系统的第一道防线,是神经炎症过程的主要效应器。在癫痫发生后与小胶质细胞激活相关的新生物标志物的发现表明,靶向特定分子可能有助于控制癫痫发作。在这项研究中,我们使用了几种生物信息学方法的组合,包括 RNA 测序,来探索癫痫病变和对照样本中的差异表达基因 (DEGs),并构建 DEGs 的蛋白质-蛋白质相互作用 (PPI) 网络,然后利用 Cytoscape 软件中的插件对其进行检查。最后,我们旨在鉴定免疫和炎症相关子网中的 10 个枢纽基因,并在海人酸诱导的癫痫小鼠模型中进行实时定量聚合酶链反应分析进行验证。9 个基因的表达模式与测序结果一致。同时,一些基因,包括 CX3CR1、CX3CL1、GPR183、FPR1、P2RY13、P2RY12 和 LPAR5,与小胶质细胞的激活和迁移有关,为癫痫的免疫治疗提供了新的候选靶点,并为进一步研究奠定了基础。

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