Introduction: COPD is the 4th most frequent cause of death globally. The principle causative agent is cigarette smoke, with up to 15% of smokers predicted to develop this disease. Smoking cessation is ineffective at halting disease progression and treatment options are restricted to symptom-alleviation and exacerbation-prophylaxis. Importantly, there are no effective treatments to halt or reverse the progression of disease. Using gene transcript analysis in patients with COPD and in an experimental model of murine COPD enables insights into the causative pathological mechanisms that underline the initiation and progression of this disease to be ascertained.
Methods: Whole genome microarray analyses were performed on lungs from mice at different time points in experimental COPD, corresponding to the initiation or progression of experimental COPD. Transcriptional profiles from these time points were compared to transcriptional profiles from human emphysematous tissue. Ingenuity Pathway Analysis (IPA) of these profiles identified key molecular pathways that are associated with COPD pathogenesis.
Results: 62 transcripts were identified in the mouse that were differentially regulated following cigarette smoke exposure at all time points investigated. 30 of these transcripts were strongly associated with emphysema in humans. IPA of these transcripts revealed that many encode proteins associated with inflammatory responses, phagocytosis, connective tissue remodelling, and oxidative stress.
Conclusion: Microarray analysis of an experimental mouse model of COPD revealed transcripts associated with the development and progression of COPD that are likely to contribute to disease pathogenesis. These transcripts showed strong correlation with genes associated with human emphysematous tissue. These transcripts may be important early biomarkers that could identify the 15% of smokers that progress to develop emphysema or be prioritised as therapeutic targets.