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

Background: Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs. Objective: To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD. Methods: We measured the expression and localizatio...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/12/10/1304
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author 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
author_facet 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
author_sort Antonino Di Stefano
collection DOAJ
description Background: Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs. Objective: To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD. 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. 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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spelling doaj.art-5d4e9ec31ecd41559bfd393d5b1760be2023-11-19T15:43:24ZengMDPI AGBiology2079-77372023-10-011210130410.3390/biology12101304Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD PatientsAntonino Di Stefano0Umberto Rosani1Stefano Levra2Isabella Gnemmi3Paola Brun4Mauro Maniscalco5Silvestro Ennio D’Anna6Vitina Carriero7Francesca Bertolini8Fabio L. M. Ricciardolo9Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell’Apparato Cardio Respiratorio, Istituti Clinici Scientifici Maugeri, IRCCS, 28010 Veruno, ItalyDepartment of Biology, University of Padova, Via Ugo Bassi 58/b, 35121 Padova, ItalyDepartment of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, 10043 Orbassano, ItalyDivisione di Pneumologia e Laboratorio di Citoimmunopatologia dell’Apparato Cardio Respiratorio, Istituti Clinici Scientifici Maugeri, IRCCS, 28010 Veruno, ItalyHistology Unit, Department of Molecular Medicine, University of Padova, 35121 Padova, ItalyDivisione di Pneumologia, Istituti Clinici Scientifici Maugeri, IRCCS, 82037 Telese, ItalyDivisione di Pneumologia, Istituti Clinici Scientifici Maugeri, IRCCS, 82037 Telese, ItalyDepartment of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, 10043 Orbassano, ItalyDepartment of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, 10043 Orbassano, ItalyDepartment of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga University Hospital, 10043 Orbassano, ItalyBackground: Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs. Objective: To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD. 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. 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.https://www.mdpi.com/2079-7737/12/10/1304TGFβBMP4chordinCRIM1BMPERBAMBI
spellingShingle 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
Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
Biology
TGFβ
BMP4
chordin
CRIM1
BMPER
BAMBI
title Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
title_full Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
title_fullStr Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
title_full_unstemmed Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
title_short Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
title_sort bone morphogenic proteins and their antagonists in the lower airways of stable copd patients
topic TGFβ
BMP4
chordin
CRIM1
BMPER
BAMBI
url https://www.mdpi.com/2079-7737/12/10/1304
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