title: Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases.
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 ofFbln1cprotected 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 ofFbln1calso 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.
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Marion A
authors.initials: MA
authors.lastname: Cooley
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Jarnicki
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Alan C-Y
authors.initials: AC
authors.lastname: Hsu
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Prema M
authors.initials: PM
authors.lastname: Nair
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Tatt Jhong
authors.initials: TJ
authors.lastname: Haw
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Fricker
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Shaan L
authors.initials: SL
authors.lastname: Gellatly
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Kim
authors.affiliation: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Inman
authors.affiliation: Woolcock Institute of Medical Research, Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Gavin
authors.initials: G
authors.lastname: Tjin
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia.
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Marjorie M
authors.initials: MM
authors.lastname: Walker
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Horvat
authors.affiliation: Woolcock Institute of Medical Research, Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia; School of Life Sciences, The University of Technology, Sydney, New South Wales, Australia.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: W Scott
authors.initials: WS
authors.lastname: Argraves
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia; Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Knight
authors.affiliation: Woolcock Institute of Medical Research, Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, New South Wales, Australia; Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, Netherlands.
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.affiliation: Priority Research for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro