Increased neutrophil gelatinase-associated lipocalin (NGAL) promotes airway remodelling in chronic obstructive pulmonary disease.
Clin Sci (Lond)
; 131(11): 1147-1159, 2017 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-28381600
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-1ß 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-3ß (GSK-3ß) 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença Pulmonar Obstrutiva Crônica
/
Remodelação das Vias Aéreas
/
Lipocalina-2
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Animals
/
Humans
/
Middle aged
Idioma:
En
Revista:
Clin Sci (Lond)
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China