PhD defence N.P. Tania
|When:||Fr 06-10-2017 at 12:45|
Developmental and pathological roles of BMP/Follistatin-like 1 in the lung
Chronic obstructive pulmonary disease (COPD) is characterized by progressive irreversible airflow limitation. By 2020, COPD will be the third major cause of death worldwide. Excessive and persistent inflammation of the airways is a major hallmark of COPD pathogenesis.
BMP signaling is crucial in embryonic lung development and adult lung homeostasis by modulating inflammation and tissue repair. The endogenous BMP inhibitor Follistatin-like 1 (Fstl1) is highly expressed in the lung. Although immunomodulatory functions of Fstl1 have been studied in various inflammatory diseases, little is known about the developmental and pathological function of Fstl1 in the lung.
This thesis provides evidence that Fstl1 protein expression is increased in airway epithelium of COPD patients and in non-COPD controls with a smoking history. Addressing the potential implications of increased Fstl1 expression in airway epithelium, we found that Fstl1 is a pro-inflammatory mediator of airway epithelial-driven inflammation. Furthermore, BMP4 negatively regulates goblet cell differentiation in adult airway epithelium, implying increased Fstl1 in COPD epithelium may contribute to goblet cell metaplasia. In addition to this role, this thesis reveals that Fstl1 is required for pulmonary vascular development postnatally, implicating a role for aberrant Fstl1 expression in vascular remodeling as well.
This thesis sheds light on the role of Fstl1 in postnatal development of pulmonary vasculature as well as pathological roles of Fstl1 in airway epithelium. Therefore, targeting Fstl1 is worth pursuing for the treatment of airway inflammation and tissue remodeling in COPD.
Promotores: Prof.dr. R. Gosens en Prof.dr. M. Schmidt