Shan Wenshan, Li Shuang, Yin Zongsheng
Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, Hefei, Anhui, China.
Front Aging Neurosci. 2023 May 18;15:1152297. doi: 10.3389/fnagi.2023.1152297. eCollection 2023.
Neuroinflammation plays an important role in spinal cord injury (SCI), and pyroptosis is inflammatory-related programmed cell death. Although neuroinflammation induced by pyroptosis has been reported in SCI, there is a lack of systematic research on SCI pyroptosis and its regulation mechanism. The purpose of this study was to systematically analyze the expression of pyroptosis-related genes (PRGs) in different SCI models and associated regulation axis by bioinformatics methods. We downloaded raw counts data of seven high-throughput sequencings and two microarray datasets from the GEO database, classified by species (rat and mouse) and SCI modes (moderate contusive model, aneurysm clip impact-compression model, and hemisection model), including mRNAs, miRNAs, lncRNAs, and circRNAs, basically covering the acute, subacute and chronic stages of SCI. We performed differential analysis by R (DEseq2) or GEO2R and found that the AIM2/NLRC4/NLRP3 inflammasome-related genes, GSDMD, IL1B, and IL18, were highly expressed in SCI. Based on the canonical NLRP3 inflammasome-mediated pyroptosis-related genes (NLRP3/PRGs), we constructed transcription factors (TFs)-NLRP3/PRGs, miRNAs- Nlrp3/PRGs and lncRNAs/circRNAs/mRNAs-miRNA- Nlrp3/PRGs (ceRNA) networks. In addition, we also predicted Traditional Chinese medicine (TCM) and small, drug-like molecules with NLRP3/PRGs as potential targets. Finally, 39 up-regulated TFs were identified, which may regulate at least two of NLRP3/PRGs. A total of 7 down-regulated miRNAs were identified which could regulate Nlrp3/PRGs. ceRNA networks were constructed including 23 lncRNAs, 3 cicrRNAs, 6 mRNAs, and 44 miRNAs. A total of 24 herbs were identified which may with two NLRP3/PRGs as potential targets. It is expected to provide new ideas and therapeutic targets for the treatment of SCI.
神经炎症在脊髓损伤（SCI）中起重要作用，而细胞焦亡是与炎症相关的程序性细胞死亡。尽管SCI中由细胞焦亡诱导的神经炎症已有报道，但对SCI细胞焦亡及其调控机制缺乏系统性研究。本研究的目的是通过生物信息学方法系统分析不同SCI模型中细胞焦亡相关基因（PRGs）的表达及相关调控轴。我们从GEO数据库下载了7个高通量测序和2个微阵列数据集的原始计数数据，按物种（大鼠和小鼠）和SCI模式（中度挫伤模型、动脉瘤夹撞击-压迫模型和半横断模型）分类，包括mRNA、miRNA、lncRNA和circRNA，基本涵盖了SCI的急性、亚急性和慢性阶段。我们用R（DEseq2）或GEO2R进行差异分析，发现AIM2/NLRC4/NLRP3炎性小体相关基因、GSDMD、IL1B和IL18在SCI中高表达。基于经典的NLRP3炎性小体介导的细胞焦亡相关基因（NLRP3/PRGs），我们构建了转录因子（TFs）-NLRP3/PRGs、miRNAs-Nlrp3/PRGs和lncRNAs/circRNAs/mRNAs-miRNA-Nlrp3/PRGs（ceRNA）网络。此外，我们还预测了以NLRP3/PRGs为潜在靶点的中药和小分子类药物。最后，鉴定出39个上调的转录因子，它们可能调控至少两个NLRP3/PRGs。共鉴定出7个下调的miRNA，它们可调控Nlrp3/PRGs。构建了包括23个lncRNA、3个circRNA、6个mRNA和44个miRNA的ceRNA网络。共鉴定出24种草药，它们可能以两个NLRP3/PRGs为潜在靶点。有望为SCI的治疗提供新思路和治疗靶点。
