Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice

We elucidated the effect of S100A4 on airway remodeling by regulating airway inflammation and epithelial–mesenchymal transition (EMT) in mouse models of asthma. Asthmatic mouse models were established by sensitization and challenged with ovalbumin (OVA). Anti-S100A4 antibody or control IgG antibody...

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Main Authors: Liu Shuang, Liu Min, Zhong Jinnan, Chen Shi, Wang Ziming, Gao Xiaoyan, Li Fajiu
Format: Article
Language:English
Published: De Gruyter 2023-10-01
Series:Open Medicine
Subjects:
Online Access:https://doi.org/10.1515/med-2022-0622
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author Liu Shuang
Liu Min
Zhong Jinnan
Chen Shi
Wang Ziming
Gao Xiaoyan
Li Fajiu
author_facet Liu Shuang
Liu Min
Zhong Jinnan
Chen Shi
Wang Ziming
Gao Xiaoyan
Li Fajiu
author_sort Liu Shuang
collection DOAJ
description We elucidated the effect of S100A4 on airway remodeling by regulating airway inflammation and epithelial–mesenchymal transition (EMT) in mouse models of asthma. Asthmatic mouse models were established by sensitization and challenged with ovalbumin (OVA). Anti-S100A4 antibody or control IgG antibody was administered daily before the OVA challenge. After the last challenge, airway inflammation and airway hyperresponsiveness were measured; lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Lung tissue sections were stained and evaluated for pathological changes. Levels of inflammatory cytokines were measured using ELISA. Levels of S100A4 and EMT markers were determined via western blotting analysis. Human bronchial epithelial cells were stimulated with 100 mg/mL house dust mites (HDMs) to evaluate the effect of S100A4 downregulation on EMT in vitro. S100A4 was increased in lung tissues and BALF from asthmatic mice. The asthmatic mice presented airway hyperresponsiveness, airway inflammation, and airway remodeling. After anti-S100A4 antibody administration, pathophysiological signs, including airway hyperresponsiveness and increased infiltration of inflammatory cells, were attenuated. Additionally, anti-S100A4 administration downregulated vimentin and α-SMA expression and upregulated E-cadherin expression in OVA-challenged mice. S100A4 downregulation also inhibited EMT process in HDM-stimulated 16HBE cells. Anti-S100A4 antibody administration alters airway remodeling by preventing EMT in mouse models of asthma.
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spelling doaj.art-839d40b639054a7cbaac63b3c5bafff42023-10-23T07:50:42ZengDe GruyterOpen Medicine2391-54632023-10-01181112310.1515/med-2022-0622Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic miceLiu Shuang0Liu Min1Zhong Jinnan2Chen Shi3Wang Ziming4Gao Xiaoyan5Li Fajiu6Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan430000, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan430000, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan430000, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan430000, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan430000, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan430000, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Jianghan University, No. 168, Hong Kong Road, Jiang’an District, Wuhan430000, Hubei, ChinaWe elucidated the effect of S100A4 on airway remodeling by regulating airway inflammation and epithelial–mesenchymal transition (EMT) in mouse models of asthma. Asthmatic mouse models were established by sensitization and challenged with ovalbumin (OVA). Anti-S100A4 antibody or control IgG antibody was administered daily before the OVA challenge. After the last challenge, airway inflammation and airway hyperresponsiveness were measured; lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Lung tissue sections were stained and evaluated for pathological changes. Levels of inflammatory cytokines were measured using ELISA. Levels of S100A4 and EMT markers were determined via western blotting analysis. Human bronchial epithelial cells were stimulated with 100 mg/mL house dust mites (HDMs) to evaluate the effect of S100A4 downregulation on EMT in vitro. S100A4 was increased in lung tissues and BALF from asthmatic mice. The asthmatic mice presented airway hyperresponsiveness, airway inflammation, and airway remodeling. After anti-S100A4 antibody administration, pathophysiological signs, including airway hyperresponsiveness and increased infiltration of inflammatory cells, were attenuated. Additionally, anti-S100A4 administration downregulated vimentin and α-SMA expression and upregulated E-cadherin expression in OVA-challenged mice. S100A4 downregulation also inhibited EMT process in HDM-stimulated 16HBE cells. Anti-S100A4 antibody administration alters airway remodeling by preventing EMT in mouse models of asthma.https://doi.org/10.1515/med-2022-0622s100a4asthmaepithelial–mesenchymal transitionairway remodeling
spellingShingle Liu Shuang
Liu Min
Zhong Jinnan
Chen Shi
Wang Ziming
Gao Xiaoyan
Li Fajiu
Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
Open Medicine
s100a4
asthma
epithelial–mesenchymal transition
airway remodeling
title Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
title_full Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
title_fullStr Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
title_full_unstemmed Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
title_short Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
title_sort anti s100a4 antibody administration alleviates bronchial epithelial mesenchymal transition in asthmatic mice
topic s100a4
asthma
epithelial–mesenchymal transition
airway remodeling
url https://doi.org/10.1515/med-2022-0622
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AT zhongjinnan antis100a4antibodyadministrationalleviatesbronchialepithelialmesenchymaltransitioninasthmaticmice
AT chenshi antis100a4antibodyadministrationalleviatesbronchialepithelialmesenchymaltransitioninasthmaticmice
AT wangziming antis100a4antibodyadministrationalleviatesbronchialepithelialmesenchymaltransitioninasthmaticmice
AT gaoxiaoyan antis100a4antibodyadministrationalleviatesbronchialepithelialmesenchymaltransitioninasthmaticmice
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