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FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

BACKGROUND: Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tri...

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Autores principales: Liu, Ying, Xu, Jiawei, Liu, Tian, Wu, Jinxiang, Zhao, Jiping, Wang, Junfei, Zou, Minfang, Cao, Lili, Liu, Xiaofei, Pan, Yun, Huang, Siyuan, Dong, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841997/
https://www.ncbi.nlm.nih.gov/pubmed/33509151
http://dx.doi.org/10.1186/s12890-021-01409-6
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author Liu, Ying
Xu, Jiawei
Liu, Tian
Wu, Jinxiang
Zhao, Jiping
Wang, Junfei
Zou, Minfang
Cao, Lili
Liu, Xiaofei
Pan, Yun
Huang, Siyuan
Dong, Liang
author_facet Liu, Ying
Xu, Jiawei
Liu, Tian
Wu, Jinxiang
Zhao, Jiping
Wang, Junfei
Zou, Minfang
Cao, Lili
Liu, Xiaofei
Pan, Yun
Huang, Siyuan
Dong, Liang
author_sort Liu, Ying
collection PubMed
description BACKGROUND: Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. METHODS: Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1(±) mice and FSTL1(flox/+) mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. RESULTS: Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1(±) mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1(±) mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1(±) mice. CONCLUSIONS: FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.
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spelling pubmed-78419972021-01-28 FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy Liu, Ying Xu, Jiawei Liu, Tian Wu, Jinxiang Zhao, Jiping Wang, Junfei Zou, Minfang Cao, Lili Liu, Xiaofei Pan, Yun Huang, Siyuan Dong, Liang BMC Pulm Med Research Article BACKGROUND: Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. METHODS: Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1(±) mice and FSTL1(flox/+) mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. RESULTS: Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1(±) mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1(±) mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1(±) mice. CONCLUSIONS: FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD. BioMed Central 2021-01-28 /pmc/articles/PMC7841997/ /pubmed/33509151 http://dx.doi.org/10.1186/s12890-021-01409-6 Text en © The Author(s) 2021 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 Article
Liu, Ying
Xu, Jiawei
Liu, Tian
Wu, Jinxiang
Zhao, Jiping
Wang, Junfei
Zou, Minfang
Cao, Lili
Liu, Xiaofei
Pan, Yun
Huang, Siyuan
Dong, Liang
FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
title FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
title_full FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
title_fullStr FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
title_full_unstemmed FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
title_short FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
title_sort fstl1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841997/
https://www.ncbi.nlm.nih.gov/pubmed/33509151
http://dx.doi.org/10.1186/s12890-021-01409-6
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