title: Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.
abstract: Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip+/-, and Fam13a-/-murine strains exposed chronically to CS. The CS-resistant Fam13a-/-mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a-/-strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.
authors.affiliation: 1 Channing Division of Network Medicine, and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jeong H
authors.initials: JH
authors.lastname: Yun
authors.affiliation: 1 Channing Division of Network Medicine, and.
authors.forename: Jarrett
authors.initials: J
authors.lastname: Morrow
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|3 The Lovelace Respiratory Research Institute, Albuquerque, New Mexico; and.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Owen
authors.affiliation: 1 Channing Division of Network Medicine, and.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Qiu
authors.affiliation: 1 Channing Division of Network Medicine, and.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Glass
authors.affiliation: 1 Channing Division of Network Medicine, and.
authors.forename: Taotao
authors.initials: T
authors.lastname: Lao
authors.affiliation: 1 Channing Division of Network Medicine, and.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|4 Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Perrella
authors.affiliation: 1 Channing Division of Network Medicine, and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: 1 Channing Division of Network Medicine, and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 1 Channing Division of Network Medicine, and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hersh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D015262:Xenobiotics
keywords: chronic obstructive pulmonary disease; cigarette smoking; gene expression; mouse model