Data_Sheet_6_Identification of canonical pyroptosis-related genes, associated regulation axis, and related traditional Chinese medicine in spinal cord injury.PDF

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.

脊髓损伤（SCI）中，神经炎症发挥着举足轻重的作用，而焦亡是一种与炎症相关的程序性细胞死亡。尽管已有研究表明在SCI中存在由焦亡诱导的神经炎症，但对于SCI中焦亡及其调控机制的系统研究仍显不足。本研究旨在通过对不同SCI模型中焦亡相关基因（PRGs）的表达进行系统分析，并结合生物信息学方法探究其相关的调控轴。我们从GEO数据库中下载了七组高通量测序和两组微阵列数据的原始计数数据，这些数据按物种（大鼠和小鼠）和SCI模式（中度挫裂模型、动脉瘤夹压模型和横切模型）分类，涵盖了SCI的急性期、亚急性期和慢性期，包括mRNA、miRNA、lncRNA和circRNA。我们利用R（DEseq2）或GEO2R进行了差异分析，发现AIM2/NLRC4/NLRP3炎症小体相关基因GSDMD、IL1B和IL18在SCI中高度表达。基于经典的NLRP3炎症小体介导的焦亡相关基因（NLRP3/PRGs），我们构建了转录因子（TFs）-NLRP3/PRGs、miRNA-Nlrp3/PRGs以及lncRNA/circRNA/mRNA-miRNA-Nlrp3/PRGs（ceRNA）网络。此外，我们还预测了具有NLRP3/PRGs作为潜在靶点的传统中药（TCM）和类似小分子药物。最终，我们确定了39个上调的TFs，这些TFs可能调节至少两个NLRP3/PRGs。共确定了7个下调的miRNAs，这些miRNAs可以调节Nlrp3/PRGs。构建的ceRNA网络包括23个lncRNA、3个cicrRNA、6个mRNA和44个miRNA。共确定了24种可能作为两个NLRP3/PRGs潜在靶点的草药。本研究预期将为SCI的治疗提供新的思路和靶点。