Gene and metabolite time-course response to cigarette smoking in mouse lung and plasma

Prolonged cigarette smoking (CS) causes chronic obstructive pulmonary disease (COPD), a prevalent serious condition that may persist or progress after smoking cessation. To provide insight into how CS triggers COPD, we investigated temporal patterns of lung transcriptome expression and systemic meta...

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Bibliographic Details
Published in:PloS one 2017-06, Vol.12 (6), p.e0178281-e0178281
Main Authors: Miller, Mikaela A, Danhorn, Thomas, Cruickshank-Quinn, Charmion I, Leach, Sonia M, Jacobson, Sean, Strand, Matthew J, Reisdorph, Nichole A, Bowler, Russell P, Petrache, Irina, Kechris, Katerina
Format: Article
Language:English
Subjects:
Age
Analysis
Animals
Bioinformatics
Biology and Life Sciences
Chronic obstructive pulmonary disease
Cigarette smoking
Cigarettes
Circadian rhythms
Coding
Critical care
Data processing
Deoxyribonucleic acid
Diagnosis
Disease
DNA
DNA repair
Drug addiction
Energy
Exons
Exposure
Female
Gene expression
Gene regulation
Genes
Genomes
Genomics
Glutathione
Goblet cells
Health aspects
Inflammation
Informatics
Liquid oxygen
Lung
Lung - metabolism
Lung diseases
Lungs
Medicine
Metabolic pathways
Metabolism
Metabolites
Metabolome
Metabolomics
Methods
Mice
Mice, Inbred C57BL
Obstructive lung disease
Oxidative stress
Pathogenesis
Phagocytosis
Pharmaceutical sciences
Pharmacy
Phosphatidylinositol
Physical Sciences
Public health
Pulmonary Disease, Chronic Obstructive - blood
Pulmonary Disease, Chronic Obstructive - etiology
Pulmonary Disease, Chronic Obstructive - genetics
Pulmonary Disease, Chronic Obstructive - metabolism
Repair
Research and Analysis Methods
Ribonucleic acid
RNA
Signal Transduction
Sleep
Smoking
Smoking - adverse effects
Smoking - blood
Smoking - genetics
Smoking - metabolism
Smoking Cessation
Studies
Tobacco smoke
Transcription
Transcription factors
Transcriptome
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Summary:Prolonged cigarette smoking (CS) causes chronic obstructive pulmonary disease (COPD), a prevalent serious condition that may persist or progress after smoking cessation. To provide insight into how CS triggers COPD, we investigated temporal patterns of lung transcriptome expression and systemic metabolome changes induced by chronic CS exposure and smoking cessation. Whole lung RNA-seq data was analyzed at transcript and exon levels from C57Bl/6 mice exposed to CS for 1- or 7 days, for 3-, 6-, or 9 months, or for 6 months followed by 3 months of cessation using age-matched littermate controls. We identified previously unreported dysregulation of pyrimidine metabolism and phosphatidylinositol signaling pathways and confirmed alterations in glutathione metabolism and circadian gene pathways. Almost all dysregulated pathways demonstrated reversibility upon smoking cessation, except the lysosome pathway. Chronic CS exposure was significantly linked with alterations in pathways encoding for energy, phagocytosis, and DNA repair and triggered differential expression of genes or exons previously unreported to associate with CS or COPD, including Lox, involved in matrix remodeling, Gp2, linked to goblet cells, and Slc22a12 and Agpat3, involved in purine and glycerolipid metabolism, respectively. CS-induced lung metabolic pathways changes were validated using metabolomic profiles of matched plasma samples, indicating that dynamic metabolic gene regulation caused by CS is reflected in the plasma metabolome. Using advanced technologies, our study uncovered novel pathways and genes altered by chronic CS exposure, including those involved in pyrimidine metabolism, phosphatidylinositol signaling and lysosome function, highlighting their potential importance in the pathogenesis or diagnosis of CS-associated conditions.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0178281