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

Hedström, Ulf (author)
Lund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lung Biology,Lund University Research Groups,AstraZeneca, Sweden
Hallgren, Oskar (author)
Lund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lung Biology,Lund University Research Groups,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
Öberg, Lisa (author)
AstraZeneca, Sweden
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Demicco, Amy (author)
AstraZeneca, Sweden
Vaarala, Outi (author)
AstraZeneca, Sweden
Westergren-Thorsson, Gunilla (author)
Lund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lung Biology,Lund University Research Groups
Zhou, Xiaohong (author)
AstraZeneca, Sweden
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 (creator_code:org_t)
2018-02-22
2018
English.
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

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