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

被引:25
作者
Hedstrom, Ulf [1 ,2 ]
Hallgren, Oskar [2 ,3 ]
Oberg, Lisa [4 ]
DeMicco, Amy [1 ]
Vaarala, Outi [4 ]
Westergren-Thorsson, Gunilla [2 ]
Zhou, Xiaohong [1 ]
机构
[1] AstraZeneca, Biosci Regenerat Dept, Resp Inflammat & Autoimmun, IMED Biotech Unit, Gothenburg, Sweden
[2] Lund Univ, Dept Expt Med Sci, Div Lung Biol, Lund, Sweden
[3] Lund Univ, Dept Clin Sci, Div Resp Med & Allergol, Lund, Sweden
[4] AstraZeneca, Biosci Immun Dept, Resp Inflammat & Autoimmun, IMED Biotech Unit, Gothenburg, Sweden
基金
瑞典研究理事会;
关键词
HEPATOCYTE GROWTH-FACTOR; OBSTRUCTIVE PULMONARY-DISEASE; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; LUNG DEVELOPMENT; DIFFERENTIATION; PROTEOGLYCANS; FIBROBLASTS; SULFATE;
D O I
10.1038/s41598-018-21727-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:13
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