Fibulin-1c regulates transforming growth factor–β activation in pulmonary tissue fibrosis

Fibulin-1c regulates transforming growth factor–β activation in pulmonary tissue fibrosis.

Full text not available from this repository.
Item Type: Article
Status: Published
Official URL: https://doi.org/10.1172/jci.insight.124529
Journal or Publication Title: JCI Insight
Volume: 4
Number: 16
Date: 2019
Divisions: UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.1172/jci.insight.124529
ISSN: 2379-3708
Date Deposited: 21 Dec 2020 23:10
Abstract:

Tissue remodeling/fibrosis is a major feature of all fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). It is underpinned by accumulating extracellular matrix (ECM) proteins. Fibulin-1c (Fbln1c) is a matricellular ECM protein associated with lung fibrosis in both humans and mice, and stabilizes collagen formation. Here we discovered that Fbln1c was increased in the lung tissues of IPF patients and experimental bleomycin-induced pulmonary fibrosis. Fbln1c-deficient (-/-) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin and tenascin-c in collagen deposits following bleomycin challenge. In a novel mechanism of fibrosis Fbln1c bound to latent transforming growth factor (TGF)-β binding protein-1 (LTBP1) to induce TGF-β activation, and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1 and LTBP1 co-localized in lung tissues from IPF patients. Thus, Fbln1c may be a novel driver of TGF-β-induced fibrosis involving LTBP1 and may be an upstream therapeutic target.

Keywords: Cell Biology; Fibrosis; Immunology.

Creators:
Creators
Email
Liu, Gang
UNSPECIFIED
Cooley, Marion A.
UNSPECIFIED
Jarnicki, Andrew G.
UNSPECIFIED
Borghuis, Theo
UNSPECIFIED
Nair, Prema M.
UNSPECIFIED
Tjin, Gavin
UNSPECIFIED
Hsu, Alan C.
UNSPECIFIED
Haw, Tatt Jhong
UNSPECIFIED
Fricker, Michael
UNSPECIFIED
Harrison, Celeste L.
UNSPECIFIED
Jones, Bernadette
UNSPECIFIED
Hansbro, Nicole G.
UNSPECIFIED
Wark, Peter A.
UNSPECIFIED
Horvat, Jay C.
UNSPECIFIED
Argraves, W. Scott
UNSPECIFIED
Oliver, Brian G.
UNSPECIFIED
Knight, Darryl A.
UNSPECIFIED
Burgess, Janette K.
UNSPECIFIED
Hansbro, Philip M.
UNSPECIFIED
Last Modified: 21 Dec 2020 23:10
URI: https://eprints.centenary.org.au/id/eprint/156

Actions (login required)

View Item View Item