Impaired differentiation of chronic obstructive pulmonary disease bronchial epithelial cells grown on bronchial scaffolds
(2021) In American Journal of Respiratory Cell and Molecular Biology 65(2). p.201-213- Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, small airway remodeling, and emphysema. Airway remodeling in patients with COPD involves both the airway epithelium and the subepithelial extracellular matrix (ECM). However, it is currently unknown how epithelial remodeling in COPD airways depends on the relative influence from inherent defects in the epithelial cells and alterations in the ECM. To address this, we analyzed global gene expression in COPD human bronchial epithelial cells (HBEC) and normal HBEC after repopulation on decellularized bronchial scaffolds derived from patients with COPD or donors without COPD. COPD HBEC grown on bronchial scaffolds showed an impaired ability to initiate... (More)
Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, small airway remodeling, and emphysema. Airway remodeling in patients with COPD involves both the airway epithelium and the subepithelial extracellular matrix (ECM). However, it is currently unknown how epithelial remodeling in COPD airways depends on the relative influence from inherent defects in the epithelial cells and alterations in the ECM. To address this, we analyzed global gene expression in COPD human bronchial epithelial cells (HBEC) and normal HBEC after repopulation on decellularized bronchial scaffolds derived from patients with COPD or donors without COPD. COPD HBEC grown on bronchial scaffolds showed an impaired ability to initiate ciliated-cell differentiation, which was evident on all scaffolds regardless of their origin. In addition, although normal HBEC were less affected by the disease state of the bronchial scaffolds, COPD HBEC showed a gene expression pattern indicating increased proliferation and a retained basal-cell phenotype when grown on COPD bronchial scaffolds compared with normal bronchial scaffolds. By using mass spectrometry, we identified 13 matrisome proteins as being differentially abundant between COPD bronchial scaffolds and normal bronchial scaffolds. These observations are consistent with COPD pathology and suggest that both epithelial cells and the ECM contribute to epithelial-cell remodeling in COPD airways.
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- author
- Hedström, Ulf LU ; Öberg, Lisa ; Vaarala, Outi ; Dellgren, Göran ; Silverborn, Martin ; Bjermer, Leif LU ; Westergren-Thorsson, Gunilla LU ; Hallgren, Oskar LU and Zhou, Xiaohong
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Airway, Chronic obstructive pulmonary disease, Epithelium, Extracellular matrix, Remodeling
- in
- American Journal of Respiratory Cell and Molecular Biology
- volume
- 65
- issue
- 2
- pages
- 13 pages
- publisher
- American Thoracic Society
- external identifiers
-
- scopus:85111769385
- pmid:33882260
- ISSN
- 1044-1549
- DOI
- 10.1165/rcmb.2019-0395OC
- language
- English
- LU publication?
- yes
- id
- 65415b31-d0d3-4f68-abfd-c6229e77e26e
- date added to LUP
- 2021-08-26 15:07:08
- date last changed
- 2024-09-22 00:11:37
@article{65415b31-d0d3-4f68-abfd-c6229e77e26e, abstract = {{<p>Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, small airway remodeling, and emphysema. Airway remodeling in patients with COPD involves both the airway epithelium and the subepithelial extracellular matrix (ECM). However, it is currently unknown how epithelial remodeling in COPD airways depends on the relative influence from inherent defects in the epithelial cells and alterations in the ECM. To address this, we analyzed global gene expression in COPD human bronchial epithelial cells (HBEC) and normal HBEC after repopulation on decellularized bronchial scaffolds derived from patients with COPD or donors without COPD. COPD HBEC grown on bronchial scaffolds showed an impaired ability to initiate ciliated-cell differentiation, which was evident on all scaffolds regardless of their origin. In addition, although normal HBEC were less affected by the disease state of the bronchial scaffolds, COPD HBEC showed a gene expression pattern indicating increased proliferation and a retained basal-cell phenotype when grown on COPD bronchial scaffolds compared with normal bronchial scaffolds. By using mass spectrometry, we identified 13 matrisome proteins as being differentially abundant between COPD bronchial scaffolds and normal bronchial scaffolds. These observations are consistent with COPD pathology and suggest that both epithelial cells and the ECM contribute to epithelial-cell remodeling in COPD airways. </p>}}, author = {{Hedström, Ulf and Öberg, Lisa and Vaarala, Outi and Dellgren, Göran and Silverborn, Martin and Bjermer, Leif and Westergren-Thorsson, Gunilla and Hallgren, Oskar and Zhou, Xiaohong}}, issn = {{1044-1549}}, keywords = {{Airway; Chronic obstructive pulmonary disease; Epithelium; Extracellular matrix; Remodeling}}, language = {{eng}}, number = {{2}}, pages = {{201--213}}, publisher = {{American Thoracic Society}}, series = {{American Journal of Respiratory Cell and Molecular Biology}}, title = {{Impaired differentiation of chronic obstructive pulmonary disease bronchial epithelial cells grown on bronchial scaffolds}}, url = {{http://dx.doi.org/10.1165/rcmb.2019-0395OC}}, doi = {{10.1165/rcmb.2019-0395OC}}, volume = {{65}}, year = {{2021}}, }