Department of Dermatology, The Yancheng Clinical College of Xuzhou Medical University, Yancheng, China.
Department of Dermatology, The First people's Hospital of Yancheng, Yancheng, China.
Exp Dermatol. 2023 Jun;32(6):840-851. doi: 10.1111/exd.14785. Epub 2023 Mar 15.
Chronic spontaneous urticaria (CSU) is a recurrent disease characterized by wheals and or angioedema, and its pathogenesis is still unclear. The microarray datasets of skin tissue from CSU patients and healthy controls were integrated and analysed in Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the NetworkAnalyst tool. Then, the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Subsequently, a protein-protein interaction (PPI) network of DEGs was constructed by STRING and the related hub genes were identified through the MOCDE tool. The potential miRNAs targeting hub genes were predicted based on the intersection of three online databases, namely TargetScanHuman, TargetBase and miRNet. Differentially expressed lncRNAs (DElncRNAs) was performed using the GEO2R tool. The potential miRNAs targeting DElncRNAs were predicted through miRNet. Finally, the shared miRNAs targeting both hub genes and DElncRNAs were used to construct an mRNA/miRNA/lncRNA regulatory network. A total of 296 DEGs were obtained, which were mainly enriched in inflammatory and immune responses. Further, 14 hub genes were identified by the PPI network of DEGs. Clinical correlation analysis showed that the mRNA expressions of S100A7, S100A8, S100A9, S100A12, IL6 and SOCS3 in CSU were positively correlated with the 7-day urticaria activity score (UAS7), and their potential diagnostic value was supported by the receiver operating characteristic curve (ROC) analysis. Five up-regulated lncRNAs in the cytoplasm were obtained by DElncRNAs analysis. The ROC analysis showed that PVT1, SNHG3 and ZBTB20 - AS1 was of potential diagnostic value for CSU. Eight shared miRNAs targeting both hub genes and DElncRNAs were identified and used to construct a competing endogenous RNA (ceRNA) network. It was found that the IL-6/miR - 149 - 5p/ZBTB20 - AS1 axis might play an important role in the activation of mast cells in CSU. IL-6 and its related regulatory molecules may be used as potential diagnostic markers and therapeutic targets for CSU.
慢性自发性荨麻疹（CSU）是一种反复发作的疾病，其特征为风团和/或血管性水肿，其发病机制尚不清楚。我们整合并分析了来自 CSU 患者和健康对照者皮肤组织的 microarray 数据集，使用 NetworkAnalyst 工具鉴定差异表达基因（DEGs）。然后，进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。接着，通过 STRING 构建 DEGs 的蛋白质-蛋白质相互作用（PPI）网络，并通过 MOCDE 工具鉴定相关枢纽基因。基于 TargetScanHuman、TargetBase 和 miRNet 三个在线数据库的交集，预测靶向枢纽基因的潜在 miRNAs。使用 GEO2R 工具进行差异表达长非编码 RNA（DElncRNA）分析。通过 miRNet 预测靶向 DElncRNA 的潜在 miRNAs。最后，使用同时靶向枢纽基因和 DElncRNA 的共享 miRNAs 构建 mRNA/miRNA/lncRNA 调控网络。共获得 296 个 DEG，主要富集于炎症和免疫反应。进一步，通过 DEGs 的 PPI 网络鉴定出 14 个枢纽基因。临床相关性分析表明，CSU 中 S100A7、S100A8、S100A9、S100A12、IL6 和 SOCS3 的 mRNA 表达与 7 天荨麻疹活动评分（UAS7）呈正相关，ROC 分析支持其潜在诊断价值。通过 DElncRNA 分析获得 5 个细胞质上调的 lncRNA。ROC 分析表明，PVT1、SNHG3 和 ZBTB20-AS1 对 CSU 具有潜在诊断价值。鉴定出 8 个同时靶向枢纽基因和 DElncRNA 的共享 miRNAs，并构建 ceRNA 网络。发现 IL-6/miR-149-5p/ZBTB20-AS1 轴可能在 CSU 中 mast 细胞激活中发挥重要作用。IL-6 及其相关调节分子可能作为 CSU 的潜在诊断标志物和治疗靶点。
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