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TGF-β signalling in COPD: Deciphering genetic and cellular susceptibilities for future therapeutic regimen.
Swiss Med. Wkly. 139, 554-563 (2009)
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the developed world and associated with a high individual and socioeconomic burden. Despite emerging preventive efforts and ongoing clinical trials, the frequency and mortality of COPD are expected to continue to rise over the next decades. COPD is defined as an irreversible expiratory airflow limitation, which is caused by various degrees of the following two main features: First, small airway disease (SAD), which includes airway inflammation and remodelling, and second, emphysema, which is characterised by airspace enlargement. The major risk factor for COPD is cigarette smoke exposure; however, the molecular mechanisms linking smoke to different COPD features on the cellular level remain elusive. The transforming growth factor (TGF)-β superfamily constitutes more than 40 members, which are essential during organ development, a process often recapitulated in chronic diseases. Emerging interest in the role of TGF-β in the pathogenesis of COPD has recently evolved, particularly since genetic studies have demonstrated an association of gene polymorphisms of the TGF-β superfamily with COPD. In addition, increased expression of TGF-β1 in COPD lungs and primary cells, such as epithelial cells, macrophages, or fibroblasts isolated from COPD specimens, was reported, suggesting an impact of TGF-β signalling on the development and progression of COPD. Thus, targeted interventions of TGF-β signalling may represent a suitable therapeutic option in COPD. In this review, we will summarise the current understanding of the impact of TGF-β in COPD pathogenesis. The review is separated into five chapters: 1) an introduction to COPD, 2) an introduction to TGF-β signalling, 3) a summary of TGF-β gene polymorphisms in COPD, 4) a summary of TGF-β signalling in small airway disease, and 5) a summary of TGF-β signalling in emphysema.
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Publication type
Article: Journal article
Document type
Review
Keywords
COPD; emphysema; chronic bronchitis;
small airway disease; transforming growth factor (TGF)-β; OBSTRUCTIVE PULMONARY-DISEASE; GROWTH-FACTOR-BETA; SMOKE-INDUCED EMPHYSEMA; ABNORMAL LUNG DEVELOPMENT; CIGARETTE-SMOKE; TRANSFORMING GROWTH-FACTOR-BETA-1; OXIDATIVE STRESS; BRONCHOPULMONARY-DYSPLASIA; FUNCTIONAL IMPAIRMENT; ALVEOLAR MACROPHAGES
ISSN (print) / ISBN
0036-7672
e-ISSN
1424-3997
Journal
Swiss Medical Weekly
Quellenangaben
Volume: 139,
Issue: 39-40,
Pages: 554-563
Publisher
EMH Schweizerischer Ärzteverlag
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Biology (LHI)