Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells
Abstract Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma. Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and...
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Nature Portfolio
2018
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oai:doaj.org-article:f43b5198fe3f450ba3479b461c43074f2021-12-02T11:40:36ZBronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells10.1038/s41598-018-21727-w2045-2322https://doaj.org/article/f43b5198fe3f450ba3479b461c43074f2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21727-whttps://doaj.org/toc/2045-2322Abstract Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma. Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM). To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals. By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM. The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients.Ulf HedströmOskar HallgrenLisa ÖbergAmy DeMiccoOuti VaaralaGunilla Westergren-ThorssonXiaohong ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) |
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Medicine R Science Q Ulf Hedström Oskar Hallgren Lisa Öberg Amy DeMicco Outi Vaarala Gunilla Westergren-Thorsson Xiaohong Zhou Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells |
description |
Abstract Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma. Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM). To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals. By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM. The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients. |
format |
article |
author |
Ulf Hedström Oskar Hallgren Lisa Öberg Amy DeMicco Outi Vaarala Gunilla Westergren-Thorsson Xiaohong Zhou |
author_facet |
Ulf Hedström Oskar Hallgren Lisa Öberg Amy DeMicco Outi Vaarala Gunilla Westergren-Thorsson Xiaohong Zhou |
author_sort |
Ulf Hedström |
title |
Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells |
title_short |
Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells |
title_full |
Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells |
title_fullStr |
Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells |
title_full_unstemmed |
Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells |
title_sort |
bronchial extracellular matrix from copd patients induces altered gene expression in repopulated primary human bronchial epithelial cells |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/f43b5198fe3f450ba3479b461c43074f |
work_keys_str_mv |
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_version_ |
1718395618253078528 |