Year: 2016
Type: article
Abstract: Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM protein involved in matrix organization, may be involved in the pathogenesis of these diseases. We found that Fbln1 was increased in COPD patients and in cigarette smoke–induced (CS-induced) experimental COPD in mice. Genetic or therapeutic inhibition of Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-α, IL-33, and CXCL1) in experimental COPD. Fbln1c –/– mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.
Source: JCI Insight
Authors: Gang Liu, Marion A. Cooley, Andrew G. Jarnicki, Alan C-Y. Hsu, Prema M. Nair, Tatt Jhong Haw, Michael Fricker, Shaan L. Gellatly, Richard Y. Kim, Mark D. Inman, Gavin Tjin, Peter A.B. Wark, Marjorie M. Walker, Jay C. Horvat, Brian G. Oliver, W. Scott Argraves, Darryl A. Knight, Janette K. Burgess, Philip M. Hansbro
Institutions: Hunter Medical Research Institute, University of Newcastle Australia, Medical University of South Carolina, McMaster University, The University of Sydney, Woolcock Institute of Medical Research, John Hunter Hospital, University of Technology Sydney, University of British Columbia, University Medical Center Groningen, University of Groningen
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
OpenAlex ID: W2439973029