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

Sci Rep. 2018 Feb 22;8(1):3502. doi: 10.1038/s41598-018-21727-w.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchi / metabolism
  • Bronchi / pathology
  • Connective Tissue Growth Factor / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Extracellular Matrix / genetics*
  • Extracellular Matrix / pathology
  • Gene Expression Regulation / genetics
  • Hepatocyte Growth Factor / genetics
  • Humans
  • Lung / metabolism*
  • Lung / pathology
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-sis / genetics
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Transcriptome / genetics*
  • Transforming Growth Factor beta1 / genetics


  • CCN2 protein, human
  • HGF protein, human
  • Proto-Oncogene Proteins c-sis
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor
  • Hepatocyte Growth Factor