Cigarette smoke decreases E-Cadherin expression downregulating FoxO3 in lung epithelial cells

Epithelial to mesenchymal transition (EMT) is implicated in lung tissue remodeling in Chronic Obstructive Pulmonary Disease (COPD). EMT is characterized by loss of epithelial junctions, including down-regulation of E-cadherin. Several signaling pathways are implicated in EMT, including TGF-β. TGF-β stimulation causes SMAD-independent activation of AKT resulting in phosphorylation and subsequent degradation of forkhead box class O3 (FoxO3). FoxO3 prevents the transcription activity of β-catenin, which controls expression of SNAIL1 and ZEB1, repressors of E-cadherin gene expression. The FoxO3 expression is reduced in the lung of COPD patients and cigarette smoke exposure contributes to this decrease. The role of FoxO3 in EMT of lung epithelial cells exposed to cigarette smoke is largely unknown.In the present study we investigated the effects of cigarette smoke and TGF-β on EMT markers in cultured lung epithelial cells and the role of FoxO3 in this process. A549 lung epithelial cells and primary bronchial epithelial cells (PBEC) were exposed to cigarette smoke extract (CSE) and TGF-β1. E-cadherin gene and protein expression, FoxO3 nuclear protein expression and SNAIL1 and ZEB1 gene expression were assessed. FoxO3 expression was silenced using siRNA and E-cadherin gene expression was evaluated. The results showed that CSE and TGF-β1: i) reduced E-cadherin gene and protein expression; ii) reduced FoxO3 nuclear protein expression in A549 and PBEC; iii...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway cell biology and immunopathology Source Type: research