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

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 imp...

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Autores principales: Klee, S., Lehmann, M., Wagner, D. E., Baarsma, H. A., Königshoff, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751539/
https://www.ncbi.nlm.nih.gov/pubmed/26867691
http://dx.doi.org/10.1038/srep20547
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author Klee, S.
Lehmann, M.
Wagner, D. E.
Baarsma, H. A.
Königshoff, M.
author_facet Klee, S.
Lehmann, M.
Wagner, D. E.
Baarsma, H. A.
Königshoff, M.
author_sort Klee, S.
collection PubMed
description 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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spelling pubmed-47515392016-02-22 WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts Klee, S. Lehmann, M. Wagner, D. E. Baarsma, H. A. Königshoff, M. Sci Rep Article 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. Nature Publishing Group 2016-02-12 /pmc/articles/PMC4751539/ /pubmed/26867691 http://dx.doi.org/10.1038/srep20547 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Klee, S.
Lehmann, M.
Wagner, D. E.
Baarsma, H. A.
Königshoff, M.
WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts
title WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts
title_full WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts
title_fullStr WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts
title_full_unstemmed WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts
title_short WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts
title_sort wisp1 mediates il-6-dependent proliferation in primary human lung fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751539/
https://www.ncbi.nlm.nih.gov/pubmed/26867691
http://dx.doi.org/10.1038/srep20547
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