Cigarette smoke alters primary human bronchial epithelial cell (PBEC) differentiation atAir-Liquid Interface (ALI): role of Oct-4, CD146 and CD105

The airway epithelium is a dynamic tissue that undergoes slow but constant renewal. Dysregulation of airway epithelial cell function related to cigarette smoke (CS) exposure plays an important role in the pathophysiology of COPD. Oct-4 is the crucial POU domain transcription factor responsible for maintaining cellular self-renewal and regeneration, and CD146 and CD105 are adhesion molecule involved in cellular proliferation, differentiation, epithelial-mesenchymal transition and tissue remodelling. Bronchial biopsy specimens (BBs) were obtained from 9 healthy controls (C) and 9 COPD. ALI cultures of PBEC from C were exposed to CS extract (CSE) for 7, 14, 21 days. Oct-4, CD105 and CD146 expression was evaluated in ALI, by Western Blot and in BBs by immunohistochemistry. Transepithelial Electrical Resistance (TEER) values measured over 7 to 21 days of differentiation decreased by 18% (5% CSE) and 29% (10% CSE) compared to untreated samples. Oct-4 expression was induced after one-week differentiation and downregulated by CSE, whilst CD105 and CD146 expression was increased by CSE. The Oct-4 epithelium immunoreactivity was reduced in COPD in comparison to C. CD146 and CD105 expression was higher in COPD than in C. Chronic CS exposure may be able to induce an altered epithelium homeostasis and regenerative capacity, as a consequence of dysregulation of differentiation mechanisms involving Oct-4 gene activity downregulation and CD146 and CD105 overexpression. The imbalance between renewal, repair processes and oxidative-stress mediated mechanisms might have a potential role in abnormal tissue remodeling and progression of COPD.