E-MTAB-1390 - Transcription profiling by array of pulmonary and nasal tissues from ApoE-/- mice to study the effect of cessation after initial exposure to cigarette smoke
Released on 19 October 2013, last updated on 3 May 2014
Although smoking cessation shows clear cardiovascular risk benefits, lung-related disease risk remains higher in former smokers than in never smokers. To better understand the factors involved in this phenomenon, ApoE-/- mice were exposed to mainstream cigarette smoke (CS) or a smoking cessation-mimicking protocol for up to six months. Analysis of bronchoalveolar lavage fluid (BALF) from CS-exposed ApoE-/- mice revealed the presence of high concentrations of mediators involved in functions ranging from inflammation to cell proliferation and tissue remodeling. Gene expression levels for many analytes found elevated in BALF were also increased in lung tissue, indicating that the inflammatory response was the result of local tissue activation and the contribution of recruited inflammatory cells. Gene set enrichment analysis (GSEA) of expression data from lungs of CS-exposed mice showed activation of pathways involved in cell proliferation and tissue remodeling and a progressive deactivation upon smoke exposure cessation. Distinct activation patterns of inflammation, complement, and xenobiotic metabolism pathways were found in nasal epithelium and lung parenchyma during CS exposure and smoking cessation. Exposure of ApoE-/- mice to CS for up to 6 months induced adaptive and inflammatory responses in the respiratory tract that were partially deactivated upon cessation. We were able to reveal molecular perturbations accompanying these changes during CS exposure and cessation. Differential CS-mediated responses of pulmonary and nasal tissues reflect common mechanisms but also the varying degrees of epithelial functional specialization along the respiratory tract. These findings provide novel clues for the identification of markers of COPD progression.
transcription profiling by array, compound treatment design, in vivo, time series design
Cigarette smoke induces molecular responses in respiratory tissues of ApoE mice that are progressively deactivated upon cessation. Boué S, De León H, Schlage WK, Peck MJ, Weiler H, Berges A, Vuillaume G, Martin F, Friedrichs B, Lebrun S, Meurrens K, Schracke N, Moehring M, Steffen Y, Schueller J, Vanscheeuwijck P, Peitsch MC, Hoeng J . Toxicology (2013), Europe PMC 24096154