Abstract：
OBJECTIVE: Chronic spontaneous urticaria (CSU) is a common and debilitating skin disease that is difficult to control with existing treatments, and the pathogenesis of CSU has not been fully revealed. The aim of this study was to explore the underlying mechanisms of CSU and identify potential treatments.
METHODS: Microarray datasets of CSU were obtained from Gene Expression Omnibus database. Differentially expressed genes between skin lesions of CSU and normal controls (LNS-DEGs) were identified, and the enrichment analyses of LNS-DEGs were performed. Hub genes of LNS-DEGs were selected by protein-protein interaction analysis. The co-expression and transcriptional regulatory networks of hub genes were conducted using GeneMANIA and TRRUST database, respectively. CIBERSORT was utilized for immune cell infiltration analysis. Experimental validation was performed by β-hexosaminidase release examination and passive cutaneous anaphylaxis (PCA) mouse model.
RESULTS: A total of 247 LNS-DEGs were identified, which were enriched in cell migration, cell chemotaxis, and inflammatory pathways such as TNF and interleukin (IL) -17 signaling pathway. Among LNS-DEGs, seven upregulated (PTGS2, CCL2, IL1B, CXCL1, IL6, VCAM1, ICAM1) and one downregulated hub gene (PECAM1) were selected. Immune infiltration analysis identified eight different immune cells, such as activated/resting mast cells and neutrophils. Furthermore, PTGS2, encoding cyclooxygenase 2 (COX2), was selected for further validation. COX2 inhibitor, celecoxib, significantly inhibited mast cell degranulation, and reduced vascular permeability and inflammatory cytokine expression in PCA mouse model.
CONCLUSIONS: PTGS2 may be a potential regulator of immunity and inflammation in CSU. Targeting PTGS2 is a new perspective for CSU treatment.
METHODS: Microarray datasets of CSU were obtained from Gene Expression Omnibus database. Differentially expressed genes between skin lesions of CSU and normal controls (LNS-DEGs) were identified, and the enrichment analyses of LNS-DEGs were performed. Hub genes of LNS-DEGs were selected by protein-protein interaction analysis. The co-expression and transcriptional regulatory networks of hub genes were conducted using GeneMANIA and TRRUST database, respectively. CIBERSORT was utilized for immune cell infiltration analysis. Experimental validation was performed by β-hexosaminidase release examination and passive cutaneous anaphylaxis (PCA) mouse model.
RESULTS: A total of 247 LNS-DEGs were identified, which were enriched in cell migration, cell chemotaxis, and inflammatory pathways such as TNF and interleukin (IL) -17 signaling pathway. Among LNS-DEGs, seven upregulated (PTGS2, CCL2, IL1B, CXCL1, IL6, VCAM1, ICAM1) and one downregulated hub gene (PECAM1) were selected. Immune infiltration analysis identified eight different immune cells, such as activated/resting mast cells and neutrophils. Furthermore, PTGS2, encoding cyclooxygenase 2 (COX2), was selected for further validation. COX2 inhibitor, celecoxib, significantly inhibited mast cell degranulation, and reduced vascular permeability and inflammatory cytokine expression in PCA mouse model.
CONCLUSIONS: PTGS2 may be a potential regulator of immunity and inflammation in CSU. Targeting PTGS2 is a new perspective for CSU treatment.
摘要：
目的：慢性自发性荨麻疹（CSU）是一种常见且使人衰弱的皮肤病，现有治疗方法难以控制。CSU的发病机制尚未完全揭示。这项研究的目的是探索CSU的潜在机制并确定潜在的治疗方法。
方法:从基因表达综合数据库获得CSU的微阵列数据集。鉴定CSU皮损与正常对照(LNS-DEGs)的差异表达基因,并进行了LNS-DEGs的富集分析。通过蛋白质-蛋白质相互作用分析选择LNS-DEGs的Hub基因。使用GeneMANIA和TRRUST数据库进行了hub基因的共表达和转录调控网络，分别。CIBERSORT用于免疫细胞浸润分析。通过β-己糖胺酶释放检查和被动皮肤过敏反应（PCA）小鼠模型进行实验验证。
结果：总共确定了247个LNS-DEG，它们富含细胞迁移，细胞趋化性，和炎症途径如TNF和白细胞介素(IL)-17信号通路。在LNS-DEG中，七个上调(PTGS2，CCL2，IL1B，选择CXCL1，IL6，VCAM1，ICAM1）和一个下调的hub基因（PECAM1）。免疫浸润分析确定了八种不同的免疫细胞，如激活/静止的肥大细胞和中性粒细胞。此外，PTGS2，编码环氧合酶2（COX2），选择进行进一步验证。COX2抑制剂，塞来昔布,显著抑制肥大细胞脱颗粒，并降低PCA小鼠模型的血管通透性和炎性细胞因子的表达。
结论：PTGS2可能是CSU免疫和炎症的潜在调节因子。靶向PTGS2是CSU治疗的新视角。
方法:从基因表达综合数据库获得CSU的微阵列数据集。鉴定CSU皮损与正常对照(LNS-DEGs)的差异表达基因,并进行了LNS-DEGs的富集分析。通过蛋白质-蛋白质相互作用分析选择LNS-DEGs的Hub基因。使用GeneMANIA和TRRUST数据库进行了hub基因的共表达和转录调控网络，分别。CIBERSORT用于免疫细胞浸润分析。通过β-己糖胺酶释放检查和被动皮肤过敏反应（PCA）小鼠模型进行实验验证。
结果：总共确定了247个LNS-DEG，它们富含细胞迁移，细胞趋化性，和炎症途径如TNF和白细胞介素(IL)-17信号通路。在LNS-DEG中，七个上调(PTGS2，CCL2，IL1B，选择CXCL1，IL6，VCAM1，ICAM1）和一个下调的hub基因（PECAM1）。免疫浸润分析确定了八种不同的免疫细胞，如激活/静止的肥大细胞和中性粒细胞。此外，PTGS2，编码环氧合酶2（COX2），选择进行进一步验证。COX2抑制剂，塞来昔布,显著抑制肥大细胞脱颗粒，并降低PCA小鼠模型的血管通透性和炎性细胞因子的表达。
结论：PTGS2可能是CSU免疫和炎症的潜在调节因子。靶向PTGS2是CSU治疗的新视角。
