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WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts.

Sci. Rep. 6:20547 (2016)
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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. IPF is characterized by epithelial cell injury and reprogramming, increases in (myo)fibroblasts, and altered deposition of extracellular matrix. The Wnt1-inducible signaling protein 1 (WISP1) is involved in impaired epithelial-mesenchymal crosstalk in pulmonary fibrosis. Here, we aimed to further investigate WISP1 regulation and function in primary human lung fibroblasts (phLFs). We demonstrate that WISP1 is directly upregulated by Transforming growth factor β1 (TGFβ1) and Tumor necrosis factor α (TNFα) in phLFs, using a luciferase-based reporter system. WISP1 mRNA and protein secretion increased in a time-and concentration-dependent manner by TGFβ1 and TNFα in phLFs, as analysed by qPCR and ELISA, respectively. Notably, WISP1 is required for TGFβ1-and TNFα-dependent induction of interleukin 6 (IL-6), a mechanism that is conserved in IPF phLFs. The siRNA-mediated WISP1 knockdown led to a significant IL-6 reduction after TGFβ1 or TNFα stimulation. Furthermore, siRNA-mediated downregulation or antibody-mediated neutralization of WISP1 reduced phLFs proliferation, a process that was in part rescued by IL-6. Taken together, these results strongly indicate that WISP1-induced IL-6 expression contributes to the pro-proliferative effect on fibroblasts, which is likely orchestrated by a variety of profibrotic mediators, including Wnts, TGFβ1 and TNFα.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Idiopathic Pulmonary-fibrosis; Wnt1-inducible Signaling Protein-1; Prostate-cancer Cells; Growth-factor; Interleukin-6 Expression; Ccn Family; Il-6; Pathway; Mice; Receptor
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Quellenangaben Volume: 6, Issue: , Pages: , Article Number: 20547 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
30503 - Chronic Diseases of the Lung and Allergies
80000 - German Center for Lung Research
Research field(s) Lung Research
PSP Element(s) G-501600-006
G-551800-001
G-501800-803
G-501800-802
Scopus ID 84958078660
Erfassungsdatum 2016-03-03