Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients

稳定期 COPD 患者下呼吸道中的骨形态发生蛋白及其拮抗剂

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作者:Antonino Di Stefano, Umberto Rosani, Stefano Levra, Isabella Gnemmi, Paola Brun, Mauro Maniscalco, Silvestro Ennio D'Anna, Vitina Carriero, Francesca Bertolini, Fabio L M Ricciardolo

Background

Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs.

Conclusions

These data show an imbalance between BMP proteins and their antagonists in the lungs of stable COPD. This imbalance may play a role in the remodeling of the airways, altering the regenerative-reparative responses of the diseased bronchioles and lung parenchyma.

Methods

We measured the expression and localization of BMPs and some relevant antagonists in bronchial biopsies of stable mild/moderate COPD (MCOPD) (n = 18), severe/very severe COPD (SCOPD) (n = 16), control smokers (CS) (n = 13), and control non-smokers (CNS) (n = 11), and in lung parenchyma of MCOPD (n = 9), CS (n = 11), and CNS (n = 9) using immunohistochemistry and transcriptome analysis, in vitro after the stimulation of the 16HBE cells.

Objective

To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD.

Results

In bronchial biopsies, BMP4 antagonists CRIM1 and chordin were increased in the bronchial epithelium and lamina propria of COPD patients. BMP4 expression was decreased in the bronchial epithelium of SCOPD and MCOPD compared to CNS. Lung transcriptomic data showed non-significant changes between groups. CRIM1 and chordin were significantly decreased in the alveolar macrophages and alveolar septa in COPD patients. External 16HBE treatment with BMP4 protein reduced the bronchial epithelial cell proliferation. Conclusions: These data show an imbalance between BMP proteins and their antagonists in the lungs of stable COPD. This imbalance may play a role in the remodeling of the airways, altering the regenerative-reparative responses of the diseased bronchioles and lung parenchyma.

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