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

Scientific Reports
Ulf HedströmXiaohong Zhou

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.

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Citations

Jun 8, 2018·European Respiratory Review : an Official Journal of the European Respiratory Society·Sarah E Gilpin, Darcy E Wagner
May 8, 2019·Stem Cells and Development·Jenny WigénGunilla Westergren-Thorsson
Jan 18, 2020·Scientific Reports·Ana B Villaseñor-AltamiranoAlejandra Medina-Rivera
Nov 12, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer M K NguyenVenkataramana K Sidhaye
Aug 6, 2019·Biotechnology Advances·Hao XingThemis R Kyriakides
Jan 8, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·Peter J BarnesMaria G Belvisi
Feb 26, 2021·Biotechnology and Bioengineering·Seyed Hossein MahfouziSeyed Hamid Safiabadi Tali
May 28, 2021·Frontiers in Pharmacology·Linda Elowsson RendinGunilla Westergren-Thorsson
Apr 22, 2021·American Journal of Respiratory Cell and Molecular Biology·Ulf HedströmXiaohong Zhou
Aug 26, 2021·Regenerative Medicine·Seyed Hossein MahfouziGhassem Amoabediny

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Datasets Mentioned

BETA
GSE107971

Methods Mentioned

BETA
Assay
RNA Assay
Reverse Transcription Polymerase Chain Reaction
RNA-Seq

Software Mentioned

Visiopharm
DESeq2
Ingenuity Pathway Analysis
QuantStudio
Visiopharm Integrator System
bcbio
hisat2
ArrayStudio
GraphPad Prism
nextgen

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