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Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells

BACKGROUND: Particulate matters (PMs) in ambient air pollution are closely related to the incidence of respiratory diseases and decreased lung function. Our previous report demonstrated that PMs-induced oxidative stress increased the expression of proinflammatory intracellular adhesion molecule-1 (I...

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Autores principales: Chen, Yu-Chen, Chuang, Tzu-Yi, Liu, Chen-Wei, Liu, Chi-Wei, Lee, Tzu-Lin, Lai, Tsai-Chun, Chen, Yuh-Lien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429884/
https://www.ncbi.nlm.nih.gov/pubmed/32799885
http://dx.doi.org/10.1186/s12989-020-00373-z
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author Chen, Yu-Chen
Chuang, Tzu-Yi
Liu, Chen-Wei
Liu, Chi-Wei
Lee, Tzu-Lin
Lai, Tsai-Chun
Chen, Yuh-Lien
author_facet Chen, Yu-Chen
Chuang, Tzu-Yi
Liu, Chen-Wei
Liu, Chi-Wei
Lee, Tzu-Lin
Lai, Tsai-Chun
Chen, Yuh-Lien
author_sort Chen, Yu-Chen
collection PubMed
description BACKGROUND: Particulate matters (PMs) in ambient air pollution are closely related to the incidence of respiratory diseases and decreased lung function. Our previous report demonstrated that PMs-induced oxidative stress increased the expression of proinflammatory intracellular adhesion molecule-1 (ICAM-1) through the IL-6/AKT/STAT3/NF-κB pathway in A549 cells. However, the role of O-PMs in epithelial-mesenchymal transition (EMT) development and pulmonary fibrosis and the related mechanisms have not been determined. The aim of this study was to investigate the effects of O-PMs on the pathogenesis of EMT and pulmonary fibrosis as well as the expression of ETS-1 and NF-κB p65, in vitro and in vivo. RESULTS: O-PMs treatment induced EMT development, fibronectin expression, and cell migration. O-PMs affected the expression of the EMT-related transcription factors NF-κB p65 and ETS-1. Interference with NF-κB p65 significantly decreased O-PMs-induced fibronectin expression. In addition, O-PMs affected the expression of fibronectin, E-cadherin, and vimentin through modulating ETS-1 expression. ATN-161, an antagonist of integrin α5β1, decreased the expression of fibronectin and ETS-1 and EMT development. EMT development and the expression of fibronectin and ETS-1 were increased in the lung tissue of mice after exposure to PMs for 7 and 14 days. There was a significant correlation between fibronectin and ETS-1 expression in human pulmonary fibrosis tissue. CONCLUSION: O-PMs can induce EMT and fibronectin expression through the activation of transcription factors ETS-1 and NF-κB in A549 cells. PMs can induce EMT development and the expression of fibronectin and ETS-1 in mouse lung tissues. These findings suggest that the ETS-1 pathway could be a novel and alternative mechanism for EMT development and pulmonary fibrosis.
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spelling pubmed-74298842020-08-18 Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells Chen, Yu-Chen Chuang, Tzu-Yi Liu, Chen-Wei Liu, Chi-Wei Lee, Tzu-Lin Lai, Tsai-Chun Chen, Yuh-Lien Part Fibre Toxicol Research BACKGROUND: Particulate matters (PMs) in ambient air pollution are closely related to the incidence of respiratory diseases and decreased lung function. Our previous report demonstrated that PMs-induced oxidative stress increased the expression of proinflammatory intracellular adhesion molecule-1 (ICAM-1) through the IL-6/AKT/STAT3/NF-κB pathway in A549 cells. However, the role of O-PMs in epithelial-mesenchymal transition (EMT) development and pulmonary fibrosis and the related mechanisms have not been determined. The aim of this study was to investigate the effects of O-PMs on the pathogenesis of EMT and pulmonary fibrosis as well as the expression of ETS-1 and NF-κB p65, in vitro and in vivo. RESULTS: O-PMs treatment induced EMT development, fibronectin expression, and cell migration. O-PMs affected the expression of the EMT-related transcription factors NF-κB p65 and ETS-1. Interference with NF-κB p65 significantly decreased O-PMs-induced fibronectin expression. In addition, O-PMs affected the expression of fibronectin, E-cadherin, and vimentin through modulating ETS-1 expression. ATN-161, an antagonist of integrin α5β1, decreased the expression of fibronectin and ETS-1 and EMT development. EMT development and the expression of fibronectin and ETS-1 were increased in the lung tissue of mice after exposure to PMs for 7 and 14 days. There was a significant correlation between fibronectin and ETS-1 expression in human pulmonary fibrosis tissue. CONCLUSION: O-PMs can induce EMT and fibronectin expression through the activation of transcription factors ETS-1 and NF-κB in A549 cells. PMs can induce EMT development and the expression of fibronectin and ETS-1 in mouse lung tissues. These findings suggest that the ETS-1 pathway could be a novel and alternative mechanism for EMT development and pulmonary fibrosis. BioMed Central 2020-08-14 /pmc/articles/PMC7429884/ /pubmed/32799885 http://dx.doi.org/10.1186/s12989-020-00373-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Yu-Chen
Chuang, Tzu-Yi
Liu, Chen-Wei
Liu, Chi-Wei
Lee, Tzu-Lin
Lai, Tsai-Chun
Chen, Yuh-Lien
Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
title Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
title_full Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
title_fullStr Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
title_full_unstemmed Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
title_short Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
title_sort particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ets-1/nf-κb-dependent pathway in lung epithelial cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429884/
https://www.ncbi.nlm.nih.gov/pubmed/32799885
http://dx.doi.org/10.1186/s12989-020-00373-z
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