title: Progranulin protects lung epithelial cells from cigarette smoking-induced apoptosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  PGRN in airway epithelial cells may regulate CS-induced AEC apoptosis and may be involved in the development of COPD.
authors.affiliation: Department of Allergy and Immunology, Asan Institute for Life Science, Seoul, Korea.
authors.forename: Kyoung Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Allergy, Asthma and COPD Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Allergy and Immunology, Asan Institute for Life Science, Seoul, Korea.
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Allergy and Immunology, Asan Institute for Life Science, Seoul, Korea.
authors.forename: Gyong Hwa
authors.initials: GH
authors.lastname: Hong
authors.affiliation: Department of Allergy and Immunology, Asan Institute for Life Science, Seoul, Korea.
authors.forename: Keun-Ai
authors.initials: KA
authors.lastname: Moon
authors.affiliation: Department of Allergy and Immunology, Asan Institute for Life Science, Seoul, Korea.
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Allergy, Asthma and COPD Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Pulmonary and Critical care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Clinical Research Center for Chronic Obstructive Airway Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yeon-Mok
authors.initials: YM
authors.lastname: Oh
authors.affiliation: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Allergy, Asthma and COPD Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyouk-Soo
authors.initials: HS
authors.lastname: Kwon
authors.affiliation: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Allergy, Asthma and COPD Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae-Bum
authors.initials: TB
authors.lastname: Kim
authors.affiliation: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Allergy, Asthma and COPD Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hee-Bom
authors.initials: HB
authors.lastname: Moon
authors.affiliation: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Allergy, Asthma and COPD Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: You Sook
authors.initials: YS
authors.lastname: Cho
mesh_terms: D000072283:A549 Cells; D000818:Animals; D017209:Apoptosis; D016022:Case-Control Studies; D000073865:Cigarette Smoking / Q000009:adverse effects*; D059865:Endoplasmic Reticulum Stress; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D000077155:Granulins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D000077153:Progranulins; D065840:Protective Factors; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D011656:Pulmonary Emphysema / Q000097:blood / Q000209:etiology / Q000378:metabolism*
chemical_list: C492314:GRN protein, human; D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: apoptosis; chronic obstructive pulmonary disease; emphysema; oxidative stress; progranulin