Transforming Growth factor beta-1 and Smad signaling has the potential to drive EMT-related changes in smokers and COPD

Introduction: TGF-b 1 has been implicated in the pathogenesis of COPD, through epithelial mesenchymal transition (EMT), which may be an intermediatory process between smoking and both airway fibrosis and lung cancer.The downstream classical TGF-b1 pathway is via the Smad transcription factor system. Methods: An immunohistochemical study was done to compare TGF-β1 and Smad 2, 3 (excitatory) and 7 (inhibitory) expression in cells and blood vessels of 3 major compartments of large airway biopsies: the basal epithelium, reticular basement membrane (Rbm) and lamina propria (LP),from patients with COPD, and in smoking and non-smoking controls. Results: TGF-b1 expression was higher generally in COPD subjects throughout the airway, (P 1 expression, was related to airflow obstruction and EMT biomarker (S100 A4) expression. Conclusion: The TGF-b1-Smad 2/3 pathway is up-regulated in smokers and COPD patients, and is linked to EMT activity and loss of lung function. Reduce in expression of inhibitory Smad-7 is also seen in COPD, and may also contribute to initiation of EMT. This study facilitates the understanding of EMT-associated pathogenesis of COPD as a result of smoking-induced intracellular downstream Smad transcriptional pathways.