title: Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer.
abstract: Chronic obstructive pulmonary disease (COPD) is a complex condition, frequently with a mix of airway and lung parenchymal damage. However, the earliest changes are in the small airways, where most of the airflow limitation occurs. The pathology of small airway damage seems to be wall fibrosis and obliteration, but the whole airway is involved in a 'field effect'. Our novel observations on active epithelial-mesenchymal transition (EMT) in the airways of smokers, particularly in those with COPD, are changing the understanding of this airway pathology and the aetiology of COPD. EMT involves a cascade of regulatory changes that destabilise the epithelium with a motile and mesenchymal epithelial cell phenotype emerging. One important manifestation of EMT activity involves up-regulation of specific key transcription factors (TFs), such as Smads, Twist, and β-catenin. Such TFs can be used as EMT biomarkers, in recognisable patterns reflecting the potential major drivers of the process; for example, TGFβ, Wnt, and integrin-linked kinase systems. Thus, understanding the relative changes in TF activity during EMT may provide rich information on the mechanisms driving this whole process, and how they may change over time and with therapy. We have sought to review the current literature on EMT and the relative expression of specific TF activity, to define the networks likely to be involved in a similar process in the airways of patients with smoking-related COPD.
authors.affiliation: NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Australia.
authors.forename: Kaosia
authors.initials: K
authors.lastname: Nowrin
authors.forename: Sukhwinder Singh
authors.initials: SS
authors.lastname: Sohal
authors.forename: Gregory
authors.initials: G
authors.lastname: Peterson
authors.forename: Rahul
authors.initials: R
authors.lastname: Patel
authors.forename: Eugene Haydn
authors.initials: EH
authors.lastname: Walters
mesh_terms: D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology* / Q000503:physiopathology; D012137:Respiratory System / Q000473:pathology* / Q000503:physiopathology; D012142:Respiratory Tract Neoplasms / Q000473:pathology* / Q000503:physiopathology
keywords: COPD; Smads; epithelial-mesenchymal transition; smoking; transcription factors; β-catenin