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

• DOI: 10.1172/jci.insight.86380
• Publication Date: 2016-06-15T18:17:40Z
• 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
• Keywords: 0301 basic medicine; 03 medical and health sciences; tissue remodeling; fibulin-1; chronic obstructive pulmonary disease (COPD); respiratory disease; 3. Good health

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.