Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Department of Rehabilitation, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Mol Med Rep. 2017 Apr;15(4):2120-2128. doi: 10.3892/mmr.2017.6231. Epub 2017 Feb 22.
Previous gene expression profiling studies of neuropathic pain (NP) following spinal cord injury (SCI) have predominantly been performed in animal models. The present study aimed to investigate gene alterations in patients with spinal cord injury and to further examine the mechanisms underlying NP following SCI. The GSE69901 gene expression profile was downloaded from the public Gene Expression Omnibus database. Samples of peripheral blood mononuclear cells (PBMCs) derived from 12 patients with intractable NP and 13 control patients without pain were analyzed to identify the differentially expressed genes (DEGs), followed by functional enrichment analysis and protein‑protein interaction (PPI) network construction. In addition, a transcriptional regulation network was constructed and functional gene clustering was performed. A total of 70 upregulated and 61 downregulated DEGs were identified in the PBMC samples from patients with NP. The upregulated and downregulated genes were significantly involved in different Gene Ontology terms and pathways, including focal adhesion, T cell receptor signaling pathway and mitochondrial function. Glycogen synthase kinase 3 β (GSK3B) was identified as a hub protein in the PPI network. In addition, ornithine decarboxylase 1 (ODC1) and ornithine aminotransferase (OAT) were regulated by additional transcription factors in the regulation network. GSK3B, OAT and ODC1 were significantly enriched in two functional gene clusters, the function of mitochondrial membrane and DNA binding. Focal adhesion and the T cell receptor signaling pathway may be significantly linked with NP, and GSK3B, OAT and ODC1 may be potential targets for the treatment of NP.
先前关于脊髓损伤后神经性疼痛（NP）的基因表达谱研究主要在动物模型中进行。本研究旨在研究脊髓损伤患者的基因改变，并进一步探讨 NP 发生的潜在机制。从公共基因表达综合数据库（GEO）中下载了 GSE69901 基因表达谱。分析了 12 例难治性 NP 患者和 13 例无疼痛对照患者的外周血单个核细胞（PBMC）样本，以鉴定差异表达基因（DEGs），然后进行功能富集分析和蛋白质-蛋白质相互作用（PPI）网络构建。此外，构建了转录调控网络并进行了功能基因聚类。在 NP 患者的 PBMC 样本中，共鉴定出 70 个上调基因和 61 个下调基因。上调和下调基因显著参与不同的基因本体论术语和途径，包括焦点粘连、T 细胞受体信号通路和线粒体功能。糖原合成酶激酶 3β（GSK3β）被鉴定为 PPI 网络中的枢纽蛋白。此外，鸟氨酸脱羧酶 1（ODC1）和鸟氨酸氨基转移酶（OAT）在调节网络中受其他转录因子的调节。GSK3β、OAT 和 ODC1 在两个功能基因簇中显著富集，即线粒体膜和 DNA 结合功能。焦点粘连和 T 细胞受体信号通路可能与 NP 显著相关，而 GSK3β、OAT 和 ODC1 可能是 NP 治疗的潜在靶点。
