The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema

Abstract Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary su...

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Autores principales:	Li Hui Tan, Karim Bahmed, Chih-Ru Lin, Nathaniel Marchetti, Sudhir Bolla, Gerard J. Criner, Steven Kelsen, Muniswamy Madesh, Beata Kosmider
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d3362e15a87d4505ac371d92e11b2b5b
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spelling	oai:doaj.org-article:d3362e15a87d4505ac371d92e11b2b5b2021-12-02T11:40:15ZThe cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema10.1038/s41598-018-21790-32045-2322https://doaj.org/article/d3362e15a87d4505ac371d92e11b2b5b2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21790-3https://doaj.org/toc/2045-2322Abstract Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ATII cells may contribute to emphysema pathogenesis.Li Hui TanKarim BahmedChih-Ru LinNathaniel MarchettiSudhir BollaGerard J. CrinerSteven KelsenMuniswamy MadeshBeata KosmiderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li Hui Tan Karim Bahmed Chih-Ru Lin Nathaniel Marchetti Sudhir Bolla Gerard J. Criner Steven Kelsen Muniswamy Madesh Beata Kosmider The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema
description	Abstract Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ATII cells may contribute to emphysema pathogenesis.
format	article
author	Li Hui Tan Karim Bahmed Chih-Ru Lin Nathaniel Marchetti Sudhir Bolla Gerard J. Criner Steven Kelsen Muniswamy Madesh Beata Kosmider
author_facet	Li Hui Tan Karim Bahmed Chih-Ru Lin Nathaniel Marchetti Sudhir Bolla Gerard J. Criner Steven Kelsen Muniswamy Madesh Beata Kosmider
author_sort	Li Hui Tan
title	The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema
title_short	The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema
title_full	The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema
title_fullStr	The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema
title_full_unstemmed	The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema
title_sort	cytoprotective role of dj-1 and p45 nfe2 against human primary alveolar type ii cell injury and emphysema
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d3362e15a87d4505ac371d92e11b2b5b
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The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema

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