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Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells

Hedström, Ulf LU ; Hallgren, Oskar LU ; Öberg, Lisa; Demicco, Amy; Vaarala, Outi; Westergren-Thorsson, Gunilla LU and Zhou, Xiaohong (2018) In Scientific Reports 8(1).
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... (More)

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.

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organization
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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85042536613
ISSN
2045-2322
DOI
10.1038/s41598-018-21727-w
language
English
LU publication?
yes
id
cc7cb18d-8aea-4959-b89d-1860af9feba2
date added to LUP
2018-03-08 08:14:07
date last changed
2018-06-24 05:21:02
@article{cc7cb18d-8aea-4959-b89d-1860af9feba2,
  abstract     = {<p>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.</p>},
  articleno    = {3502},
  author       = {Hedström, Ulf and Hallgren, Oskar and Öberg, Lisa and Demicco, Amy and Vaarala, Outi and Westergren-Thorsson, Gunilla and Zhou, Xiaohong},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells},
  url          = {http://dx.doi.org/10.1038/s41598-018-21727-w},
  volume       = {8},
  year         = {2018},
}