空气细颗粒物通过C3a/C3aR轴诱导鼻黏膜上皮间质转化

doi:10.3969/j.issn.1006-7795.2026.04.009

首都医科大学学报 ›› 2026, Vol. 47 ›› Issue (4): 692-699.doi: 10.3969/j.issn.1006-7795.2026.04.009

空气细颗粒物通过C3a/C3aR轴诱导鼻黏膜上皮间质转化

梁爽^1,2,闫冰^1,2,李颖^1,2,王成硕^1,2,张罗^1,2,3*

1.首都医科大学附属北京同仁医院耳鼻咽喉头颈外科耳鼻咽喉头颈科学教育部重点实验室（首都医科大学），北京 100730；2.北京市耳鼻咽喉科研究所，过敏性疾病北京实验室（北京市教育委员会），慢性鼻病新药及诊断技术研发北京市重点实验室，北京 100005；3. 首都医科大学附属北京同仁医院变态反应（鼻过敏）科，北京 100730

收稿日期:2026-04-08 修回日期:2026-05-05 出版日期:2026-08-21 发布日期:2026-07-26
通讯作者: 张罗 E-mail:dr.luozhang@139.com
基金资助:
国家重点研发计划项目（2023YFC2410200），国家自然科学基金项目（82471135，82401325，82025010)，北京市卫生系统高层次公共卫生技术人才建设项目（学科骨干－03－03）。

Fine particulate matter induces epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the C3a/C3aR axis

Liang Shuang^1,2, Yan Bing^1,2,Li Ying ^1,2,Wang Chengshuo^1,2, Zhang Luo ^1,2,3*

1.Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otorhinolaryngology Head and Neck Surgery (Capital Medical University), Ministry of Education, Beijing 100730, China; 2.Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing Institute of Otolaryngology, Beijing 100005, China；, China; 3.Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Received:2026-04-08 Revised:2026-05-05 Online:2026-08-21 Published:2026-07-26
Supported by:
This work was supported by grants from the National Key R&D Program of China (2023YFC2410200), National Natural Science Foundation of China （82471135，82401325，82025010), Special Funds for the Construction of High-level Public Health Technical Talents (Backbone of Academic Research-03-03).

摘要/Abstract

摘要： 目的探究补体成分3（complement component 3a，C3a）/C3a受体（C3a receptor，C3aR）轴在空气细颗粒物（fine particulate matter，PM_2.5）诱导慢性鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps，CRSwNP）上皮间质转化（epithelial-mesenchymal transition，EMT）中的作用。方法人原代鼻黏膜上皮细胞（human primary nasal epithelial cells，HPNECs）暴露于50 μg/mL PM_2.5后，利用免疫荧光法检测细胞中上皮标志物E-钙黏蛋白和间质标志物波形蛋白表达。获取公共数据集（GSE220165和GSE36830）分析钙黏蛋白1和波形蛋白表达，并利用Spearman相关性分析C3aR与EMT相关分子［钙黏蛋白1、波形蛋白、锌指E-box 结合同源盒蛋白2(zinc finger E-box binding homeobox 2, ZEB2）］、基质金属蛋白酶9［matrix metallopeptidase 9, MMP9)］的相关性。蛋白免疫印迹法检测C3a和C3aR蛋白水平。并利用C3aR拮抗剂处理HPNECs，利用免疫荧光和蛋白免疫印迹法检测EMT相关分子的表达。结果 PM_2.5暴露下调HPNECs中E-钙黏蛋白表达，上调波形蛋白表达，与公共数据集分析结果一致。PM_2.5暴露增加HPNECs中C3a和C3aR的蛋白水平。C3aR表达与EMT相关分子ZEB2（r=0.497, P=0.014 4）、MMP9（r=0.409, P=0.048 5）呈正相关，与波形蛋白呈正相关趋势，但差异无统计学意义（r=0.377, P=0.069 9）。而C3aR拮抗剂处理可缓解PM2.5诱导的E-钙黏蛋白下调及波形蛋白、ZEB2和MMP9表达增加。结论 PM_2.5可通过补体C3a/C3aR轴促进CRSwNP鼻黏膜上皮发生EMT。

关键词: 空气细颗粒物, 慢性鼻窦炎伴鼻息肉, 人原代鼻上皮细胞, 补体成分C3, 补体成分C3a受体拮抗剂, 上皮间质转化

Abstract: Objective To investigate the role of the complement C3a/C3aR axis in PM_2.5-induced epithelial-mesenchymal transition (EMT) in chronic rihinosinusitis with nasal polyps (CRSwNP).Methods The expression levels of the epithelial marker E-cadherin and mesenchymal marker vimentin were detected by immunofluorescence staining in 50 μg/mL PM_2.5-treated human primary nasal epithelial cells (HPNECs) from patients with CRSwNP. Public datasets (GSE220165 and GSE36830) were obtained to analyzed the expression of cadherin 1 and VIM, and Spearman' correlation analysis between the complement component 3a receptor (C3aR) and EMT-related molecules ［cadherin 1, VIM, zinc finger E-box binding homeobox 2 (ZEB2), and matrix metallopeptidase 9 (MMP9)］ were performed. Protein levels of C3a and C3aR in PM_2.5-treated HPNECs were analyzed by Western blotting. EMT markers were examined in HPNECs after C3aR antagonist (C3aRA) treatment using immunofluorescence and Western blotting assays.Results PM_2.5 downregulated cadherin 1 and upregulated vimentin expression in HPNECs, in agreement with previously published transcriptomic data (GSE220165). PM2.5 increased both C3a and its receptor C3aR levels in HPNECs. C3aR expression positively correlated with the EMT-related molecules ZEB2 (r=0.497, P=0.014 4) and MMP9 (r=0.409, P=0.048). Although its correlation with VIM exhibited a positive trend, it did not reach statistical significance (r=0.377, P=0.069 9). Blocking the C3a/C3aR axis with C3aRA partially alleviated PM_2.5-induced downregulation of E-cadherin and upregulation of vimentin, ZEB2, and MMP9 in HPNECs.Conclusion PM_2.5 could induce EMT via activation of the C3a/C3aR axis in CRSwNP.

Key words: fine particulate matter (PM_2.5), chronic rhinosinusitis with nasal polyps (CRSwNP), human primary nasal epithelial cells, complement component 3, complement component 3a receptor antagonist, epithelial-mesenchymal transition

中图分类号:

R765

梁爽, 闫冰, 李颖, 王成硕, 张罗. 空气细颗粒物通过C3a/C3aR轴诱导鼻黏膜上皮间质转化[J]. 首都医科大学学报, 2026, 47(4): 692-699.

Liang Shuang, Yan Bing, Li Ying , Wang Chengshuo, Zhang Luo . Fine particulate matter induces epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the C3a/C3aR axis[J]. Journal of Capital Medical University, 2026, 47(4): 692-699.

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空气细颗粒物通过C3a/C3aR轴诱导鼻黏膜上皮间质转化

Fine particulate matter induces epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the C3a/C3aR axis

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