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Progranulin protects lung epithelial cells from cigarette smoking‐induced apoptosis
Author(s) -
Lee Kyoung Young,
Park SoYoung,
Park Sunjoo,
Hong Gyong Hwa,
Moon KeunAi,
Kim YouSun,
Oh YeonMok,
Kwon HyoukSoo,
Kim TaeBum,
Moon HeeBom,
Cho You Sook
Publication year - 2017
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.13023
Subject(s) - medicine , lung , apoptosis , cigarette smoking , pathology , cancer research , genetics , biology
Background and objective Emphysema 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 . Methods First, 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. Results Our 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 .