Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

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...

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Published inJCI insight Vol. 1; no. 9
Main Authors Liu, Gang, Cooley, Marion A, Jarnicki, Andrew G, Hsu, Alan C-Y, Nair, Prema M, Haw, Tatt Jhong, Fricker, Michael, Gellatly, Shaan L, Kim, Richard Y, Inman, Mark D, Tjin, Gavin, Wark, Peter A B, Walker, Marjorie M, Horvat, Jay C, Oliver, Brian G, Argraves, W Scott, Knight, Darryl A, Burgess, Janette K, Hansbro, Philip M
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 16.06.2016
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Summary: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 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 also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-α, IL-33, and CXCL1) in experimental COPD. 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.
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Authorship note: G. Liu, M.A. Cooley, and A.G. Jarnicki contributed equally to this work. W. Scott Argraves is deceased.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.86380