Progranulin protects lung epithelial cells from cigarette smoking-induced apoptosis

Background and objectiveEmphysema is characterized by irreversible destruction of alveolar walls with distal air space enlargement. Cigarette smoke (CS) is considered a major risk factor for emphysematous changes in COPD. Progranulin (PGRN), a glycoprotein induced by CS, has been reported to participate in apoptosis. However, the precise role of PGRN in emphysema is currently unknown. This study aimed to evaluate the role of PGRN in human alveolar epithelial cells (AECs) in response to CS. MethodsFirst, PGRN expression was assessed in a mouse model of CS-induced emphysema and in AECs after exposure to CS extract (CSE). Then, the effect of PGRN on CSE-mediated apoptosis was determined under PGRN silencing or overexpressing conditions. To investigate the functional mechanism of PGRN, endoplasmic reticulum (ER) stress markers and the mitogen-activated protein kinase (MAPK) pathway were also evaluated in the CSE-exposed cells. Finally, PGRN expression levels in sera and peripheral blood mononuclear cells (PBMCs) were measured and compared between patients with COPD and healthy subjects. ResultsOur results revealed that PGRN expression was elevated in CS-exposed mouse lungs and CSE-treated AECs. CSE-induced cellular apoptosis was significantly increased in PGRN-knockdown AECs and decreased in PGRN-overexpression cells. The activation of ER stress-associated molecules correlated with PGRN expression levels. Compared with healthy controls, COPD patients exhibited significantly lower PGRN serum levels and higher PBMC intracellular PGRN levels. Conclusion PGRN in airway epithelial cells may regulate CS-induced AEC apoptosis and may be involved in the development of COPD. In a previous study, it was shown that progranulin (PGRN) inhibits apoptosis. However, the precise role of PGRN and whether it attenuates apoptosis in alveolar epithelial cells (AECs) has not been clarified. Here, we demonstrate that PGRN protects AECs from apoptosis induced by cigarette smoke.