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Increased neutrophil gelatinase-associated lipocalin (NGAL) promotes airway remodelling in chronic obstructive pulmonary disease

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Title: Increased neutrophil gelatinase-associated lipocalin (NGAL) promotes airway remodelling in chronic obstructive pulmonary disease
Authors: Wang, Y
Jia, M
Yan, X
Cao, L
Barnes, PJ
Adcock, IM
Huang, M
Yao, X
Item Type: Journal Article
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 enhanced NGAL mRNA 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.
Issue Date: 22-May-2017
Date of Acceptance: 5-Apr-2017
URI: http://hdl.handle.net/10044/1/49447
DOI: https://dx.doi.org/10.1042/CS20170096
ISSN: 0143-5221
Publisher: PORTLAND PRESS LTD
Start Page: 1147
End Page: 1159
Journal / Book Title: CLINICAL SCIENCE
Volume: 131
Issue: 11
Copyright Statement: © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 093080/Z/10/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
EPITHELIAL-MESENCHYMAL TRANSITION
OXIDATIVE STRESS
CIGARETTE-SMOKE
PERIPHERAL-BLOOD
OZONE-EXPOSURE
INFLAMMATION
CELLS
EXPRESSION
FIBROSIS
ASTHMA
airway remodeling
copd
epithelial-to-mesenchymal transition
neutrophils
Aged
Airway Remodeling
Animals
Basement Membrane
Bronchi
Bronchoalveolar Lavage Fluid
Cell Movement
Cell Proliferation
Cells, Cultured
Disease Models, Animal
Epithelial-Mesenchymal Transition
Gene Expression Regulation
Humans
Inflammation Mediators
Intercellular Signaling Peptides and Proteins
Lipocalin-2
Lung
Mice, Inbred C57BL
Middle Aged
Neutrophils
Ozone
Pulmonary Disease, Chronic Obstructive
RNA, Messenger
Smoking
Wnt Signaling Pathway
11 Medical And Health Sciences
Cardiovascular System & Hematology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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