Emphysema is characterized by irreversible destruction of alveolar walls with enlargement of distal airspaces. Cigarette smoke (CS) is considered as a main causative factor for the development of emphysematous change in chronic obstructive airway disease. Progranulin (PGRN) has been reported to be induced in response to various stimuli including CS. Recently, PGRN is reported to participate in apoptosis process that is well known cause of alveolar wall destruction. However, the role of PGRN in emphysema is currently unknown.
We tested if there is a regulatory role of PGRN in human alveolar epithelial cells exposed to CSE.
Both protein and mRNA expression levels of PGRN were measured in A549 cells after exposure to cigarette smoke extract (CSE). The effect of PGRN on CSE-mediated apoptosis was determined by using flowcytometry analysis with annexin V and PI staining in PGRN-silencing A549 cells.
PGRN expression was increased in A549 cells treated with CSE. A significant increase of active caspase-3 and active PARP expression was detected in PGRN-silencing A549 cells after CSE exposure. Frequency of apoptotic cell death was also significantly increased in PGRN knock-down cells.
PGRN plays a potential role in the development of emphysema probably by preventing apoptosis of alveolar cells.