Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells

The role of the epithelial–mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure o...

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Autores principales:	Tzu-Yin Chen, Chia-Hao Liu, Tsung-Hsien Chen, Mei-Ru Chen, Shan-Wen Liu, Pinpin Lin, Kurt Ming-Chao Lin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adipose-derived stem cell conditioned medium epithelial–mesenchymal transition (EMT) cigarette smoke extract COPD TGF-β1 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/874685df20384481b1ee505f93526afc
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spelling	oai:doaj.org-article:874685df20384481b1ee505f93526afc2021-11-11T17:27:40ZConditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells10.3390/ijms2221120691422-00671661-6596https://doaj.org/article/874685df20384481b1ee505f93526afc2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12069https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The role of the epithelial–mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-β1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-β1 treatment. CSE or TGF-β1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.Tzu-Yin ChenChia-Hao LiuTsung-Hsien ChenMei-Ru ChenShan-Wen LiuPinpin LinKurt Ming-Chao LinMDPI AGarticleadipose-derived stem cellconditioned mediumepithelial–mesenchymal transition (EMT)cigarette smoke extractCOPDTGF-β1Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12069, p 12069 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adipose-derived stem cell conditioned medium epithelial–mesenchymal transition (EMT) cigarette smoke extract COPD TGF-β1 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	adipose-derived stem cell conditioned medium epithelial–mesenchymal transition (EMT) cigarette smoke extract COPD TGF-β1 Biology (General) QH301-705.5 Chemistry QD1-999 Tzu-Yin Chen Chia-Hao Liu Tsung-Hsien Chen Mei-Ru Chen Shan-Wen Liu Pinpin Lin Kurt Ming-Chao Lin Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells
description	The role of the epithelial–mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-β1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-β1 treatment. CSE or TGF-β1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.
format	article
author	Tzu-Yin Chen Chia-Hao Liu Tsung-Hsien Chen Mei-Ru Chen Shan-Wen Liu Pinpin Lin Kurt Ming-Chao Lin
author_facet	Tzu-Yin Chen Chia-Hao Liu Tsung-Hsien Chen Mei-Ru Chen Shan-Wen Liu Pinpin Lin Kurt Ming-Chao Lin
author_sort	Tzu-Yin Chen
title	Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells
title_short	Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells
title_full	Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells
title_fullStr	Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells
title_full_unstemmed	Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells
title_sort	conditioned media of adipose-derived stem cells suppresses sidestream cigarette smoke extract induced cell death and epithelial-mesenchymal transition in lung epithelial cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/874685df20384481b1ee505f93526afc
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Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells

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