MicroRNAs in Asthma and COPD; from biomarkers to regulators of disease pathogenesis

Asthma and COPD are chronic inflammatory lung diseases. In both disease, the combination of genetic susceptibility and exposure to environmental factors plays a major role in the development and exacerbations. The current treatment options reduce symptoms but until now there is no cure for asthma or COPD. In order to identify novel treatment strategies, there is an urgent need to get more insights in the mechanisms of asthma and COPD.In this thesis we investigated the role of microRNAs (miRNAs) in the pathogenesis of asthma and COPD. MiRNAs are small RNA molecules that can bind to messenger RNA (mRNA), which is involved in the translation of hereditary information in the DNA into proteins. We hypothesized that miRNAs are involved in the pathogenesis of asthma and COPD by controlling inflammatory processes. Additionally, we hypothesized that miRNAs expression in asthma and COPD patients is altered and that miRNAs can function as biomarkers to distinguish between disease severity, inflammatory phenotypes or predict the response to therapy. We observed that asthma and COPD patients have altered miRNA profiles in lung and airways compared to controls. We hereby identified potential biomarkers for obstructive lung diseases, such as miR-320d and miR-26a. Furthermore, we demonstrated that miR-223 and miR-320d are involved in the regulation of inflammatory responses in asthma and COPD models. Therefore, it may be possible that dysregulated expression and impaired function of these miRNAs contribute to the pathogenesis of asthma and COPD. This may provide novel therapeutic strategies in the treatment of obstructive pulmonary diseases