title: Increased neutrophil gelatinase-associated lipocalin (NGAL) promotes airway remodelling in chronic obstructive pulmonary disease.
abstract: Airway remodelling is an important component of chronic obstructive pulmonary disease (COPD). Neutrophil gelatinase-associated lipocalin (NGAL) from neutrophils may drive COPD epithelial-mesenchymal transition (EMT). NGAL expression was quantified in the lungs of COPD patients and bronchoalveolar lavage fluid (BALF) of ozone-treated mice. Reticular basement membrane (RBM) thickness and E-cadherin and α-smooth muscle actin (α-SMA) expression were determined in mice airways. Effects of cigarette smoke extract (CSE) and inflammatory factors on NGAL expression in human neutrophils as well as the effects of NGAL on airway structural cells was assessed. NGAL was mainly distributed in neutrophils and enhanced in lung tissues of both COPD patients and BALF of ozone-treated mice. We showed decreased E-cadherin and increased α-SMA expression in bronchial epithelium and increased RBM thickness in ozone-treated animals.In vitro, CSE, IL-1β and IL-17 enhancedNGALmRNA expression in human neutrophils. NGAL, in turn, down-regulated the expression of E-cadherin and up-regulated α-SMA expression in 16HBE cells via the WNT/glycogensynthase kinase-3β (GSK-3β) pathway. Furthermore, NGAL promoted the proliferation and migration of human bronchial smooth muscle cells (HASMCs). The present study suggests that elevated NGAL promotes COPD airway remodelling possibly through altered EMT. NGAL may be a potential target for reversing airway obstruction and remodelling in COPD.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.|Department of Respiratory Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou 570100, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Cao
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, U.K.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, U.K.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China yaoxin@njmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
mesh_terms: D000368:Aged; D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D000071068:Lipocalin-2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010126:Ozone; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D012907:Smoking / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology
chemical_list: C501126:DKK1 protein, human; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D000071068:Lipocalin-2; D012333:RNA, Messenger; D010126:Ozone
keywords: airway remodeling; copd; epithelial-to-mesenchymal transition; neutrophils