@article{9a24afba018243f693dcaa24c283fe6b,
title = "Fibulin-1c regulates transforming growth factor–β activation in pulmonary tissue fibrosis",
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 patients with IPF and experimental bleomycin-induced pulmonary fibrosis. Fbln1c-deficient (Fbln1c–/–) 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 potentially novel mechanism of fibrosis, Fbln1c bound to latent 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. Fbln1c and LTBP1 colocalized in lung tissues from patients with IPF. Thus, Fbln1c may be a novel driver of TGF-β–induced fibrosis involving LTBP1 and may be an upstream therapeutic target.",
author = "Gang Liu and Cooley, {Marion A.} and Jarnicki, {Andrew G.} and Theo Borghuis and Nair, {Prema M.} and Gavin Tjin and Hsu, {Alan C.} and Haw, {Tatt Jhong} and Michael Fricker and Harrison, {Celeste L.} and Bernadette Jones and Hansbro, {Nicole G.} and Wark, {Peter A.} and Horvat, {Jay C.} and {Scott Argraves}, W. and Oliver, {Brian G.} and Knight, {Darryl A.} and Burgess, {Janette K.} and Hansbro, {Philip M.}",
note = "Funding Information: This work was supported as follows. GL was supported by Lung Foundation Australia/Lizotte Family Research Award. The NIH supported WSA and MAC. AGJ was supported by Lung Foundation of Australia/Boehringer Ingelheim COPD Research Fellowship. BGO and JKB were supported by National Health and Medical Research Council (NHMRC) Career Development Fellowships. JKB was supported by a University of Groningen/European Union Rosalind Franklin Fellowship. PMH received fellowships and grants from NHMRC of Australia (NHMRC 1079187) and the Brawn Foundation, Faculty of Health and Medicine, the University of Newcastle. This work is dedicated to the memory of W. Scott Argraves, who passed away during the completion of this study. Publisher Copyright: Copyright: {\textcopyright} 2019, American Society for Clinical Investigation.",
year = "2019",
month = jul,
day = "25",
doi = "10.1172/jci.insight.124529",
language = "English (US)",
volume = "4",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "16",
}