Project description:Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disorder primarily induced by cigarette smoking, and characterized by persistent airflow limitation. The mouse represents an important model for studying COPD pathologies such as lung emphysema. In this respect, a number of mechanistic studies have been performed, however the approaches were mostly focused on single gene analysis or characterization of cellular, inflammatory or histopathological changes without attempting a more comprehensive interpretation. In the present study we aimed at applying systems biology approach to identify genome-wide molecular mechanisms indicative of cigarette smoke (CS)-induced lung emphysema. The lung transcriptomes of five mouse models (C57BL/6, ApoE-/-, A/J, CD1, and Nrf2-/-), that are known to be susceptible to CS-induced emphysema development, were analyzed following prolonged (5-6 months) CS exposure. The investigation resulted in the confirmation of many existing mechanistic explanations underlying smoke-induced lung emphysema, including increased transcriptional activity of NF-?B, and increased levels of TNF-a, IFN-g, and IL-1b. More importantly, we predicted mechanisms without currently well-documented roles, including increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1 and N-cor, and increased IL-17 cytokine expression, and reduced protein expression of ITGB6 and CFTR. We also corroborated, by using targeted proteomic approaches, several predictions such as reduced expression of ITGB6 and increased expression of BRCA1, C/EBPs, PU.1, TNF-a, IL-1b or CSF2. We believe this study will provide more insights into better understanding of CS-induced molecular processes underlying emphysema development in mice that may eventually be relevant in humans.

2014-11-28 | E-MTAB-2756 | biostudies-arrayexpress

The role of matrix metalloproteinase-9 in cigarette smoke-induced emphysema.

Project description: Not available

| S-EPMC3086754 | biostudies-literature

Ebselen prevents cigarette smoke-induced gastrointestinal dysfunction in mice.

Project description: Not available

| S-EPMC7676466 | biostudies-literature

Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice.

Project description: Not available

| S-EPMC4742374 | biostudies-literature

Pulmonary epithelial neuropilin-1 deletion enhances development of cigarette smoke-induced emphysema.

Project description: Not available