Chronic electronic cigarette use elicits molecular changes related to pulmonary pathogenesis

The relative safety of chronic exposure to electronic cigarette (e-cig) aerosol remains unclear in terms of lung pathogenesis. Therefore, this study aims to evaluate gene/protein biomarkers, which are associated with cigarette-induced pulmonary injury in animals chronically exposed to nicotine containing e-cig aerosol. C57BL/6 J mice were randomly assigned to three exposure groups: e-cig, tobacco cigarette smoke, and filtered air. Lung tissues and/or paraffin embedded slides were used to evaluate gene and/or protein expressions of the CYP450 metabolism (CYP1A1, CYP2A5, and CYP3A11), oxidative stress (Nrf2, SOD1), epithelial-mesenchymal transition (E-cadherin and vimentin), lung pathogenesis (AhR), and survival/apoptotic pathways (p-AKT, BCL-XL, p53, p21, and CRM1). Expressions of E-cadherin and CRM1 were significantly decreased, while CYP1A1, AhR, SOD1 and BCL-XL were significantly upregulated in the e-cig group compared to the control (p < 0.05). Nuclear sub-cellular localization of p53, evaluated by immunohistochemistry staining, in bronchiolar tissues was higher in the e-cig group (25.3 ± 2.7%) as compared to controls (12.1 ± 1.8%) (p < 0.01). Although the biomarkers responses were not identical, in general, the responses had similar qualitative trends between the e-cig and cigarette groups. As these related molecular changes are involved in the pathogenesis of cigarette-induced lung injury, the possibility exists that e-cigs can produce a similar outcome. Although further investigation is warranted, e-cigs are unlikely to be considered as safe in terms of pulmonary health.