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Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by defective extracellular matrix (ECM) turnover as a result of prolonged cigarette smoking. Fibroblasts have a central role in ECM turnover. The TGFβ induced Smad pathway provides intracellular signals to regulate ECM product...

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Autores principales: Zandvoort, Andre, Postma, Dirkje S, Jonker, Marnix R, Noordhoek, Jacobien A, Vos, Johannes TWM, Timens, Wim
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613883/
https://www.ncbi.nlm.nih.gov/pubmed/19087346
http://dx.doi.org/10.1186/1465-9921-9-83
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author Zandvoort, Andre
Postma, Dirkje S
Jonker, Marnix R
Noordhoek, Jacobien A
Vos, Johannes TWM
Timens, Wim
author_facet Zandvoort, Andre
Postma, Dirkje S
Jonker, Marnix R
Noordhoek, Jacobien A
Vos, Johannes TWM
Timens, Wim
author_sort Zandvoort, Andre
collection PubMed
description BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by defective extracellular matrix (ECM) turnover as a result of prolonged cigarette smoking. Fibroblasts have a central role in ECM turnover. The TGFβ induced Smad pathway provides intracellular signals to regulate ECM production. We address the following hypothesis: fibroblasts have abnormal expression of genes in the Smad pathway in COPD, resulting in abnormal proteoglycan modulation, the ground substance of ECM. METHODS: We compared gene expression of the Smad pathway at different time points after stimulation with TGFβ, TNF or cigarette smoke extract (CSE) in pulmonary fibroblasts of GOLD stage II and IV COPD patients, and controls. RESULTS: Without stimulation, all genes were similarly expressed in control and COPD fibroblasts. TGFβ stimulation: downregulation of Smad3 and upregulation of Smad7 occurred in COPD and control fibroblasts, indicating a negative feedback loop upon TGFβ stimulation. CSE hardly influenced gene expression of the TGFβ-Smad pathway in control fibroblasts, whereas it reduced Smad3 and enhanced Smad7 gene expression in COPD fibroblasts. Furthermore, decorin gene expression decreased by all stimulations in COPD but not in control fibroblasts. CONCLUSION: Fibroblasts of COPD patients and controls differ in their regulation of the Smad pathway, the contrast being most pronounced under CSE exposure. This aberrant responsiveness of COPD fibroblasts to CSE might result in an impaired tissue repair capability and is likely important with regard to the question why only a subset of smokers demonstrates an excess ECM destruction under influence of cigarette smoking.
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spelling pubmed-26138832009-01-06 Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD Zandvoort, Andre Postma, Dirkje S Jonker, Marnix R Noordhoek, Jacobien A Vos, Johannes TWM Timens, Wim Respir Res Research BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by defective extracellular matrix (ECM) turnover as a result of prolonged cigarette smoking. Fibroblasts have a central role in ECM turnover. The TGFβ induced Smad pathway provides intracellular signals to regulate ECM production. We address the following hypothesis: fibroblasts have abnormal expression of genes in the Smad pathway in COPD, resulting in abnormal proteoglycan modulation, the ground substance of ECM. METHODS: We compared gene expression of the Smad pathway at different time points after stimulation with TGFβ, TNF or cigarette smoke extract (CSE) in pulmonary fibroblasts of GOLD stage II and IV COPD patients, and controls. RESULTS: Without stimulation, all genes were similarly expressed in control and COPD fibroblasts. TGFβ stimulation: downregulation of Smad3 and upregulation of Smad7 occurred in COPD and control fibroblasts, indicating a negative feedback loop upon TGFβ stimulation. CSE hardly influenced gene expression of the TGFβ-Smad pathway in control fibroblasts, whereas it reduced Smad3 and enhanced Smad7 gene expression in COPD fibroblasts. Furthermore, decorin gene expression decreased by all stimulations in COPD but not in control fibroblasts. CONCLUSION: Fibroblasts of COPD patients and controls differ in their regulation of the Smad pathway, the contrast being most pronounced under CSE exposure. This aberrant responsiveness of COPD fibroblasts to CSE might result in an impaired tissue repair capability and is likely important with regard to the question why only a subset of smokers demonstrates an excess ECM destruction under influence of cigarette smoking. BioMed Central 2008 2008-12-16 /pmc/articles/PMC2613883/ /pubmed/19087346 http://dx.doi.org/10.1186/1465-9921-9-83 Text en Copyright © 2008 Zandvoort et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Zandvoort, Andre
Postma, Dirkje S
Jonker, Marnix R
Noordhoek, Jacobien A
Vos, Johannes TWM
Timens, Wim
Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD
title Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD
title_full Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD
title_fullStr Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD
title_full_unstemmed Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD
title_short Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD
title_sort smad gene expression in pulmonary fibroblasts: indications for defective ecm repair in copd
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613883/
https://www.ncbi.nlm.nih.gov/pubmed/19087346
http://dx.doi.org/10.1186/1465-9921-9-83
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