Estrogen Receptor-α Exacerbates EGF-Inducing Airway Remodeling and Mucus Production in Bronchial Epithelium of Asthmatics.

IF 4.1 2区医学 Q2 ALLERGY

Allergy, Asthma & Immunology Research Pub Date : 2023-09-01 Epub Date: 2023-04-26 DOI:10.4168/aair.2023.15.5.614

Lu Qin, Junqing Yue, Mingzhou Guo, Cong Zhang, Xiaoyu Fang, Shengding Zhang, Wenxue Bai, Xiansheng Liu, Min Xie

{"title":"Estrogen Receptor-α Exacerbates EGF-Inducing Airway Remodeling and Mucus Production in Bronchial Epithelium of Asthmatics.","authors":"Lu Qin, Junqing Yue, Mingzhou Guo, Cong Zhang, Xiaoyu Fang, Shengding Zhang, Wenxue Bai, Xiansheng Liu, Min Xie","doi":"10.4168/aair.2023.15.5.614","DOIUrl":null,"url":null,"abstract":"Purpose: Although estrogen receptors (ERs) signal pathways are involved in the pathogenesis and development of asthma, their expressions and effects remain controversial. This study aimed to investigate the expressions of ERα and ERβ as well as their mechanisms in airway remodeling and mucus production in asthma.Methods: The expressions of ERα and ERβ in the airway epithelial cells of bronchial biopsies and induced sputum cells were examined by immunohistochemistry. The associations of ERs expressions with airway inflammation and remodeling were evaluated in asthmatic patients. In vitro, the regulations of ERs expressions in human bronchial epithelial cell lines were examined using western blot analysis. The epidermal growth factor (EGF)-mediated ligand-independent activation of ERα and its effect on epithelial-mesenchymal transitions (EMTs) were investigated in asthmatic epithelial cells by western blot, immunofluorescent staining, and quantitative real-time polymerase chain reaction.Results: ERα and ERβ were expressed on both bronchial epithelial cells and induced sputum cells, and the expressions showed no sex difference. Compared to controls, male asthmatic patients had higher levels of ERα on the bronchial epithelium, and there were cell-specific expressions of ERα and ERβ in induced sputum. The expression of ERα in the airway epithelium was inversely correlated to forced expiratory volume in 1 second (FEV1) % and FEV1/forced vital capacity. Severe asthmatic patients had significantly greater levels of ERα in the airway epithelium than mild-moderate patients. ERα level was positively correlated with the thickness of the subepithelial basement membrane and airway epithelium. In vitro, co-stimulation of interleukin (IL)-4 and EGF increased the expression of ERα and promoted its nuclear translocation. EGF activated the phosphorylation of ERα via extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways. ERα knockdown alleviated EGF-mediated EMTs and mucus production in airway epithelial cells of asthma.Conclusions: ERα contributes to asthmatic airway remodeling and mucus production through the EGF-mediated ligand-independent pathway.","PeriodicalId":7547,"journal":{"name":"Allergy, Asthma & Immunology Research","volume":"15 5","pages":"614-635"},"PeriodicalIF":4.1000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/47/aair-15-614.PMC10570787.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy, Asthma & Immunology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4168/aair.2023.15.5.614","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: Although estrogen receptors (ERs) signal pathways are involved in the pathogenesis and development of asthma, their expressions and effects remain controversial. This study aimed to investigate the expressions of ERα and ERβ as well as their mechanisms in airway remodeling and mucus production in asthma.

Methods: The expressions of ERα and ERβ in the airway epithelial cells of bronchial biopsies and induced sputum cells were examined by immunohistochemistry. The associations of ERs expressions with airway inflammation and remodeling were evaluated in asthmatic patients. In vitro, the regulations of ERs expressions in human bronchial epithelial cell lines were examined using western blot analysis. The epidermal growth factor (EGF)-mediated ligand-independent activation of ERα and its effect on epithelial-mesenchymal transitions (EMTs) were investigated in asthmatic epithelial cells by western blot, immunofluorescent staining, and quantitative real-time polymerase chain reaction.

Results: ERα and ERβ were expressed on both bronchial epithelial cells and induced sputum cells, and the expressions showed no sex difference. Compared to controls, male asthmatic patients had higher levels of ERα on the bronchial epithelium, and there were cell-specific expressions of ERα and ERβ in induced sputum. The expression of ERα in the airway epithelium was inversely correlated to forced expiratory volume in 1 second (FEV1) % and FEV1/forced vital capacity. Severe asthmatic patients had significantly greater levels of ERα in the airway epithelium than mild-moderate patients. ERα level was positively correlated with the thickness of the subepithelial basement membrane and airway epithelium. In vitro, co-stimulation of interleukin (IL)-4 and EGF increased the expression of ERα and promoted its nuclear translocation. EGF activated the phosphorylation of ERα via extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways. ERα knockdown alleviated EGF-mediated EMTs and mucus production in airway epithelial cells of asthma.

Conclusions: ERα contributes to asthmatic airway remodeling and mucus production through the EGF-mediated ligand-independent pathway.

Abstract Image

查看原文本刊更多论文

雌激素受体-α增强EGF诱导哮喘患者气道重塑和支气管上皮粘液产生。

目的：尽管雌激素受体（ER）信号通路参与哮喘的发病机制和发展，但其表达和作用仍存在争议。本研究旨在探讨ERα和ERβ在哮喘气道重塑和粘液生成中的表达及其机制。方法：应用免疫组织化学方法检测ERα和ERβ在支气管活检气道上皮细胞和诱导痰细胞中的表达。在哮喘患者中评估了ERs表达与气道炎症和重塑的关系。在体外，使用蛋白质印迹分析检测了人支气管上皮细胞系中ERs表达的调节。采用蛋白质印迹、免疫荧光染色和实时定量聚合酶链反应研究了表皮生长因子（EGF）介导的ERα配体非依赖性激活及其对哮喘上皮细胞上皮-间质转化（EMTs）的影响。结果：ERα和ERβ在支气管上皮细胞和诱导痰细胞上均有表达，且表达无性别差异。与对照组相比，男性哮喘患者支气管上皮上的ERα水平较高，诱导痰中有ERα和ERβ的细胞特异性表达。ERα在气道上皮中的表达与1秒用力呼气量（FEV1）%和FEV1/用力肺活量呈负相关。重度哮喘患者气道上皮ERα水平明显高于轻度-中度哮喘患者。ERα水平与上皮下基底膜和气道上皮厚度呈正相关。在体外，白细胞介素-4和EGF的共同刺激增加了ERα的表达并促进其核转位。EGF通过细胞外信号调节激酶和c-Jun N-末端激酶途径激活ERα的磷酸化。ERα的敲除减轻了哮喘气道上皮细胞中EGF介导的EMT和粘液的产生。结论：ERα通过EGF介导的配体非依赖性途径参与哮喘气道重塑和粘液产生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Allergy, Asthma & Immunology Research ALLERGY-IMMUNOLOGY

CiteScore

6.10

自引率

6.80%

发文量

审稿时长

>12 weeks

期刊介绍： The journal features cutting-edge original research, brief communications, and state-of-the-art reviews in the specialties of allergy, asthma, and immunology, including clinical and experimental studies and instructive case reports. Contemporary reviews summarize information on topics for researchers and physicians in the fields of allergy and immunology. As of January 2017, AAIR do not accept case reports. However, if it is a clinically important case, authors can submit it in the form of letter to the Editor. Editorials and letters to the Editor explore controversial issues and encourage further discussion among physicians dealing with allergy, immunology, pediatric respirology, and related medical fields. AAIR also features topics in practice and management and recent advances in equipment and techniques for clinicians concerned with clinical manifestations of allergies and pediatric respiratory diseases.