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

Abstract

COPD is an inflammatory disease characterized by persistent airflow limitation largely associated with airway remodeling. NGAL is a lipocalin family member involved in cell growth and proliferation. We explored the role of NGAL on airway remodeling. The expression and distribution of NGAL was quantified in the lungs of COPD patients and in a murine model. The effect of cigarette smoke extract (CSE) on NGAL expression as well as the effects of recombinant NGAL protein on human bronchial epithelial cells (HBEs) and bronchial smooth muscle cells(HASMCs) was also examined. Enhanced NGAL expression was found in lung neutrophils and alveolar macrophages of COPD patients[Fig 1]. NGAL expression was also elevated in inflammatory cells of ozone-treated mouse lung and bronchoalveolar lavage fluid (BALF). CSE induced NGAL mRNA expression in human neutrophils and alveolar macrophages in a time- and concentration-dependent manner. NGAL down-regulated the mRNA and protein expression of the epithelial marker E-cadherin and up-regulated α-smooth muscle actin (α-SMA) expression in HBEs via the WNT3/β-catenin pathway. NGAL promoted HASMCs proliferation and migration in a concentration-dependent manner. Our findings suggest that NGAL released by COPD neutrophils and macrophages may play an important role in airway remodeling and airflow limitation in COPD.