Overexpression of FOXA2 attenuates cigarette smoke-induced cellular senescence and lung inflammation through inhibition of the p38 and Erk1/2 MAPK pathways

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible and progressive airflow limitation and encompasses varying degrees of chronic obstructive bronchitis and emphysema. Our previous study showed that Forkhead box protein A2 (FOXA2) is involved in cigarette smoke (CS)-induced squamous metaplasia. However, the contribution of FOXA2 activity to CS-induced cellular senescence and lung inflammation remains largely unknown. Here, we report that FOXA2 was underexpressed in CS-exposed mouse lungs, and decreased expression of FOXA2 was related to cell senescence and inflammation. Subsequent investigation suggested that FOXA2 is an anti-senescence factor in lung that is involved in inflammatory responses. Furthermore, FOXA2 overexpression delayed CSE-induced senescence and inflammation, which correlated with regulation of the p38 and Erk1/2 MAPK signaling pathways by CSE-induced FOXA2 downregulation. Collectivelly, these findings reveal a protective role for FOXA2 as a regulator of cell senescence and inflammation during COPD.

Automated summary

FOXA2 is underexpressed in CS-exposed mouse lungs, associated with cell senescence and inflammation. Overexpression of FOXA2 delays senescence and inflammation, potentially through regulation of the p38 and Erk1/2 MAPK signaling pathways.