- Title
- Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases
- Creator
- Liu, Gang; Cooley, Marion A.; 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.; Jarnicki, Andrew G.; Hsu, Alan C-Y.; Nair, Prema M.; Haw, Tatt Jhong; FRICKER, Michael; Gellatly, Shaan L.; Kim, Richard Y.; Inman, Mark D.
- Relation
- Journal of Clinical Investigation Insight Vol. 1, Issue 9, no. e86380
- Publisher Link
- http://dx.doi.org/10.1172/jci.insight.86380
- Publisher
- American Society for Clinical Investigation
- Resource Type
- journal article
- Date
- 2016
- Description
- 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-a, 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.
- Subject
- fibulin-1; respiratory disease; tissue remodeling; chronic obstructive pulmonary disease (COPD)
- Identifier
- http://hdl.handle.net/1959.13/1348904
- Identifier
- uon:30281
- Identifier
- ISSN:2379-3708
- Language
- eng
- Full Text
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