COPD is characterized by a not fully reversible and usually progressive airflow limitation, which is associated with an abnormal inflammatory response of the lungs to mostly cigarette smoke (CS), causing obstruction of the small airways and alveolar destruction (i.e. emphysema). COPD is currently the fourth leading cause of death worldwide and causes a substantial economic and social burden. Pharmacotherapy
for COPD decreases symptoms; however, none of the existing medications has been shown to modify the accelerated decline in lung function.
MicroRNAs (miRNAs) are endogenous, small non-coding RNAs with a regulatory function on gene
expression. By directly inhibiting protein translation or by degrading messenger RNA, miRNAs can interact with hundreds of genes simultaneously and regulate several developmental and physiologic processes.
The aim of this translational research project is to elucidate the role of miRNAs in the pathogenesis of COPD and to evaluate their therapeutic potential in this disease. Therefore, we will investigate aberrant miRNA profiles in CS-exposed mice and human bronchial epithelial cells and in patients with COPD.
Integrative genomics will be used to screen for candidate miRNAs that play important roles in crucial pathways in COPD pathogenesis. Finally, we aim at gathering evidence that restoration of the normal miRNA profile has therapeutic value in a pre-clinical model of COPD.