Huang W Q, Huang Z Z, Lai X P, Li Y, Chen X H, Wu H T, Chang L H, Zhang Y N, Zhang G H
Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Jun 7;57(6):692-698. doi: 10.3760/cma.j.cn115330-20210731-00504.
To preliminarily analyze the expression of angiotensin-converting enzyme 2 (ACE2) and to investigate its potential regulatory mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP). Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from February 2020 to May 2021 were selected, including 17 males and 6 females, aging from 23 to 66 years old. Expression of ACE2 was evaluated via immunohistochemical staining in controls with non-chronic rhinosinusitis, non-eosinophilic CRSwNP (non-ECRSwNP), and eosinophilic CRSwNP (ECRSwNP) tissue, respectively. Correlations between ACE2 and the indicated Th1/Th2-related cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-25, IL-33, TSLP and periostin) were analyzed based on GSE72713 dataset. Protein-protein interaction (PPI) network was constructed via string database, immune infiltration of GSE72713 dataset was evaluated using cibersort algorithm. ACE2 was comprehensively analyzed by microRNA regulatory network, gene set enrichment analysis (GSEA) and pharmacological analysis. Statistical analysis was performed using GraphPad 7.0 and SPSS 20.0 software. ACE2 was up-regulated in non-ECRSwNP compared with ECRSwNP. Microarray analysis showed that ACE2 was positively correlated with IFN-γ while inversely correlated with IL-5, IL-13 and periostin significantly. Analysis of immune infiltration suggested that ACE2 expression correlated positively with the number of M1 macrophage while negatively with M2 macrophage. GSEA demonstrated that interferon-related signaling pathways were up-regulated in non-ECRSwNP, and miRNA-200B/miRNA-200C/miRNA-429 pathways targeting ACE2 were enriched in ECRSwNP. Results of pharmacological analysis indicated that ampicillin was able to promote the expression of ACE2 whereas acetaminophen could down regulated the expression of ACE2. Expression pattern of ACE2 is varied in non-ECRSwNP and ECRSwNP, which may be related to the different infiltration of indicated cytokines and different regulatory pathways of miRNA.
初步分析血管紧张素转换酶2（ACE2）的表达，并探讨其在伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）中的潜在调控机制。选取2020年2月至2021年5月在中山大学附属第三医院接受鼻内镜手术的患者，其中男性17例，女性6例，年龄23至66岁。分别通过免疫组织化学染色评估非慢性鼻-鼻窦炎对照组、非嗜酸性CRSwNP（非ECRSwNP）和嗜酸性CRSwNP（ECRSwNP）组织中ACE2的表达。基于GSE72713数据集分析ACE2与所示Th1/Th2相关细胞因子（IFN-γ、IL-4、IL-5、IL-13、IL-25、IL-33、TSLP和骨膜蛋白）之间的相关性。通过STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络，使用Cibersort算法评估GSE72713数据集的免疫浸润情况。通过微小RNA调控网络、基因集富集分析（GSEA）和药理学分析对ACE2进行综合分析。使用GraphPad 7.0和SPSS 20.0软件进行统计分析。与ECRSwNP相比，ACE2在非ECRSwNP中上调。微阵列分析表明，ACE2与IFN-γ呈正相关，而与IL-5、IL-13和骨膜蛋白呈显著负相关。免疫浸润分析表明，ACE2表达与M1巨噬细胞数量呈正相关，与M2巨噬细胞数量呈负相关。GSEA表明，干扰素相关信号通路在非ECRSwNP中上调，而靶向ACE2的miRNA-200B/miRNA-200C/miRNA-429通路在ECRSwNP中富集。药理学分析结果表明，氨苄青霉素能够促进ACE2的表达，而对乙酰氨基酚可下调ACE2的表达。ACE2在非ECRSwNP和ECRSwNP中的表达模式不同，这可能与所示细胞因子的不同浸润和微小RNA的不同调控途径有关。
