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Respir Res. 2008 Dec 16;9:83. doi: 10.1186/1465-9921-9-83.

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

Author information

1
Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. a.zandvoort@med.umcg.nl

Abstract

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 TGFbeta 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 TGFbeta, 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. TGFbeta stimulation: downregulation of Smad3 and upregulation of Smad7 occurred in COPD and control fibroblasts, indicating a negative feedback loop upon TGFbeta stimulation. CSE hardly influenced gene expression of the TGFbeta-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.

PMID:
19087346
PMCID:
PMC2613883
DOI:
10.1186/1465-9921-9-83
[Indexed for MEDLINE]
Free PMC Article

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