Wang Kai, Yi Duan, Yu Zhuoyin, Zhu Bin, Li Shuiqing, Liu Xiaoguang
Department of Pain Medicine Center, Peking University Third Hospital, Beijing, China.
Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
Front Neurosci. 2020 May 20;14:488. doi: 10.3389/fnins.2020.00488. eCollection 2020.
The reactivity enhancement of pain sensitive neurons in the nervous system is a feature of the pathogenesis for neuropathic pain (NP), yet the underlying mechanisms need to be fully understood. In this study, we made an attempt to clarify the NP-related hub genes and signaling pathways so as to provide effective diagnostic and therapeutic methods toward NP.
Microarray expression profile GSE30691 including the mRNA-seq data of the spared nerve injury (SNI)-induced NP rats was accessed from the GEO database. Then, genes associated with NP development were screened using differential analysis along with random walk with restart (RWR). GO annotation and KEGG pathway analyses were performed to explore the biological functions and signaling pathways where the genes were activated. Afterward, protein-protein interaction (PPI) analysis and GO analysis were conducted to further identify the hub genes which showed an intimate correlation with NP development.
Totally 94 genes associated with NP development were screened by differential analysis and RWR analysis, and they were observed to be predominantly enriched in hormone secretion and transport, cAMP signaling pathway and other NP occurrence associated functions and pathways. Thereafter, the 94 genes were subjected to PPI analysis to find the genes much more associated with NP and a functional module composed of 48 genes were obtained. 8 hub genes including C3, C1qb, Ccl2, Cxcl13, Timp1, Fcgr2b, Gal, and Lyz2 were eventually identified after further association and functional enrichment analyses, and the expression of these 8 genes were all higher in SNI rats by comparison with those in Sham rats.
Based on the data collected from GEO database, this study discovered 8 hub genes that were closely related to NP occurrence and development, which help to provide potent theoretical basis for NP treatment.
神经系统中疼痛敏感神经元的反应性增强是神经性疼痛（NP）发病机制的一个特征，但其潜在机制仍需充分了解。在本研究中，我们试图阐明与NP相关的枢纽基因和信号通路，以便为NP提供有效的诊断和治疗方法。
从GEO数据库获取微阵列表达谱GSE30691，其中包括 spared nerve injury（SNI）诱导的NP大鼠的mRNA-seq数据。然后，使用差异分析和带重启的随机游走（RWR）筛选与NP发展相关的基因。进行GO注释和KEGG通路分析，以探索基因被激活的生物学功能和信号通路。之后，进行蛋白质-蛋白质相互作用（PPI）分析和GO分析，以进一步鉴定与NP发展密切相关的枢纽基因。
通过差异分析和RWR分析共筛选出94个与NP发展相关的基因，观察到它们主要富集于激素分泌和转运、cAMP信号通路以及其他与NP发生相关的功能和通路。此后，对这94个基因进行PPI分析，以找到与NP关联更强的基因，并获得了一个由48个基因组成的功能模块。经过进一步的关联和功能富集分析，最终鉴定出8个枢纽基因，包括C3、C1qb、Ccl2、Cxcl13、Timp1、Fcgr2b、Gal和Lyz2，与假手术组大鼠相比，这8个基因在SNI大鼠中的表达均更高。
基于从GEO数据库收集的数据，本研究发现了8个与NP发生和发展密切相关的枢纽基因，这有助于为NP治疗提供有力的理论依据。
