Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions
Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions
复制标题
加权基因共表达网络分析揭示了与背根神经节神经病理性疼痛相关的特定模块和中枢基因
DOI：
10.1042/bsr20191511
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发表时间：
2019-11-13
影响因子：
4
通讯作者：
Li, Xiang
中科院分区：
文献类型：
--
作者：
Cheng, Nan;Zhang, Zheng;Li, Xiang
摘要神经病理性疼痛是一种常见的，使人衰弱的临床问题。在这里，加权基因共表达网络分析（WGCNA）被用来识别与神经病理性疼痛相关的特定模块和枢纽基因。从ArrayExpress数据库（E-MTAB-2260）下载由胫神经横断（TNT）诱导的神经病大鼠模型的微阵列数据集，包括来自TNT模型（n=7）和假手术（n=8）大鼠的背根神经节（DRG）组织。通过WGCNA软件包鉴定共表达网络模块。构建了蛋白质相互作用（PPI）网络，并将网络中连接度最高的节点确定为枢纽基因。共鉴定了1739个基因和7个模块。最重要的模块是棕色模块，它包含215个基因，主要与防御反应的生物过程（BP）和钙离子结合的分子功能相关。此外，C-C基序趋化因子配体2（Ccl 2）、Fos和金属蛋白酶组织抑制剂1（Timp 1）分别被确定为PPI网络和两个子网络中的枢纽基因。体内实验证实，TNT可上调DRG和脊髓组织中Ccl 2、Fos和Timp 1的mRNA和蛋白水平。本研究提供了新的见解神经病理性疼痛的分子机制的背景下，周围神经损伤。
Abstract Neuropathic pain is a common, debilitating clinical issue. Here, the weighted gene co-expression network analysis (WGCNA) was used to identify the specific modules and hub genes that are related to neuropathic pain. The microarray dataset of a neuropathic rat model induced by tibial nerve transection (TNT), including dorsal root ganglion (DRG) tissues from TNT model (n=7) and sham (n=8) rats, was downloaded from the ArrayExpress database (E-MTAB-2260). The co-expression network modules were identified by the WGCNA package. The protein–protein interaction (PPI) network was constructed, and the node with highest level of connectivity in the network were identified as the hub gene. A total of 1739 genes and seven modules were identified. The most significant module was the brown module, which contained 215 genes that were primarily associated with the biological process (BP) of the defense response and molecular function of calcium ion binding. Furthermore, C–C motif chemokine ligand 2 (Ccl2), Fos and tissue inhibitor of metalloproteinase 1 (Timp1) which were identified as the hub genes in the PPI network and two subnetworks separately. The in vivo studies validated that mRNA and protein levels of Ccl2, Fos and Timp1 were up-regulated in DRG and spinal cord tissues after TNT. The present study offers novel insights into the molecular mechanisms of neuropathic pain in the context of peripheral nerve injury.