Chronic obstructive pulmonary disease (COPD) is a major cause of mortality throughout the world. COPD is characterized by an abnormal inflammatory reaction of the lungs to cigarette smoking, resulting in airflow limitation due to destruction of lung tissue (= emphysema) and structural changes in and around the airways. Therapies or drugs that slow down the accelerated decline in lung function in patients with COPD are still lacking. Insights into the mechanisms that underlie the inflammatory reaction and subsequent structural changes in COPD are incomplete. The main objective of this research project is to explore the functional role of the transforming growth factor (TGF)-beta superfamily in the development of COPD. The TGF-beta superfamily is a large family of proteins that is involved in diverse physiological processes including lung development and lung disease. The family comprises TGF-beta, activins, bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs). In this project, we will focus on the members BMP-6, GDF-15 and TGF-beta2, based on their dysregulated expression in COPD and their known role in inflammation and tissue remodelling. For this purpose, we will study the expression of BMP-6, GDF-15 and TGF-beta2 in lung tissue of patients with COPD (and healthy controls). Furthermore, we will expose mice – deficient for BMP-6, GDF-15 and TGF-beta2 – to cigarette smoke and investigate whether this affects the development of COPD hallmarks.