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Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis

BACKGROUND: CD248 or Endosialin is a transmembrane molecule expressed in stromal cells binding to extracellular matrix (ECM) components. It has been previously implicated in kidney fibrosis, rheumatoid arthritis as well as in tumour-stromal interactions. This study investigates the role of CD248 in...

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Autores principales: Bartis, Domokos, Crowley, Louise E., D’Souza, Vijay K., Borthwick, Lee, Fisher, Andrew J., Croft, Adam P., Pongrácz, Judit E., Thompson, Richard, Langman, Gerald, Buckley, Christopher D., Thickett, David R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832513/
https://www.ncbi.nlm.nih.gov/pubmed/27080864
http://dx.doi.org/10.1186/s12890-016-0211-7
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author Bartis, Domokos
Crowley, Louise E.
D’Souza, Vijay K.
Borthwick, Lee
Fisher, Andrew J.
Croft, Adam P.
Pongrácz, Judit E.
Thompson, Richard
Langman, Gerald
Buckley, Christopher D.
Thickett, David R.
author_facet Bartis, Domokos
Crowley, Louise E.
D’Souza, Vijay K.
Borthwick, Lee
Fisher, Andrew J.
Croft, Adam P.
Pongrácz, Judit E.
Thompson, Richard
Langman, Gerald
Buckley, Christopher D.
Thickett, David R.
author_sort Bartis, Domokos
collection PubMed
description BACKGROUND: CD248 or Endosialin is a transmembrane molecule expressed in stromal cells binding to extracellular matrix (ECM) components. It has been previously implicated in kidney fibrosis, rheumatoid arthritis as well as in tumour-stromal interactions. This study investigates the role of CD248 in the pathogenesis of fibrotic diseases in Idiopathic Pulmonary Fibrosis (IPF). METHODS: CD248 quantitative immunohistochemistry (IHC) was performed on lung samples from 22 IPF patients and its expression was assayed in cultured pulmonary fibroblasts and epithelial cells. Effects of CD248 silencing was evaluated on fibroblast proliferation and myofibroblast differentiation. RESULTS: IHC revealed strong CD248 expression in mesenchymal cells of normal lung structures such as pleura and adventitia but not in epithelium. Fibrotic areas showed markedly stronger staining than unaffected lung tissue. The extent of CD248 staining showed a significant negative correlation to lung function parameters FEV1, FVC, TLC, and TLCO (r2 > 0 · 35, p < 0 · 01). CD248 protein levels were significantly greater in IPF-derived lung fibroblasts vs normal lung fibroblasts (p < 0 · 01) and CD248 silencing significantly reduced the proliferation of lung fibroblasts, but did not affected myofibroblast differentiation. CONCLUSION: We conclude that CD248 overexpression is possibly involved in the pathogenesis of IPF and it has potential as a disease severity marker. Given that CD248 ligands are collagen type I, IV and fibronectin, we hypothesise that CD248 signalling represents a novel matrix-fibroblast interaction that may be a potential therapeutic target in IPF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-016-0211-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-48325132016-04-16 Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis Bartis, Domokos Crowley, Louise E. D’Souza, Vijay K. Borthwick, Lee Fisher, Andrew J. Croft, Adam P. Pongrácz, Judit E. Thompson, Richard Langman, Gerald Buckley, Christopher D. Thickett, David R. BMC Pulm Med Research Article BACKGROUND: CD248 or Endosialin is a transmembrane molecule expressed in stromal cells binding to extracellular matrix (ECM) components. It has been previously implicated in kidney fibrosis, rheumatoid arthritis as well as in tumour-stromal interactions. This study investigates the role of CD248 in the pathogenesis of fibrotic diseases in Idiopathic Pulmonary Fibrosis (IPF). METHODS: CD248 quantitative immunohistochemistry (IHC) was performed on lung samples from 22 IPF patients and its expression was assayed in cultured pulmonary fibroblasts and epithelial cells. Effects of CD248 silencing was evaluated on fibroblast proliferation and myofibroblast differentiation. RESULTS: IHC revealed strong CD248 expression in mesenchymal cells of normal lung structures such as pleura and adventitia but not in epithelium. Fibrotic areas showed markedly stronger staining than unaffected lung tissue. The extent of CD248 staining showed a significant negative correlation to lung function parameters FEV1, FVC, TLC, and TLCO (r2 > 0 · 35, p < 0 · 01). CD248 protein levels were significantly greater in IPF-derived lung fibroblasts vs normal lung fibroblasts (p < 0 · 01) and CD248 silencing significantly reduced the proliferation of lung fibroblasts, but did not affected myofibroblast differentiation. CONCLUSION: We conclude that CD248 overexpression is possibly involved in the pathogenesis of IPF and it has potential as a disease severity marker. Given that CD248 ligands are collagen type I, IV and fibronectin, we hypothesise that CD248 signalling represents a novel matrix-fibroblast interaction that may be a potential therapeutic target in IPF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-016-0211-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-04-14 /pmc/articles/PMC4832513/ /pubmed/27080864 http://dx.doi.org/10.1186/s12890-016-0211-7 Text en © Bartis et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Bartis, Domokos
Crowley, Louise E.
D’Souza, Vijay K.
Borthwick, Lee
Fisher, Andrew J.
Croft, Adam P.
Pongrácz, Judit E.
Thompson, Richard
Langman, Gerald
Buckley, Christopher D.
Thickett, David R.
Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis
title Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis
title_full Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis
title_fullStr Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis
title_full_unstemmed Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis
title_short Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis
title_sort role of cd248 as a potential severity marker in idiopathic pulmonary fibrosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832513/
https://www.ncbi.nlm.nih.gov/pubmed/27080864
http://dx.doi.org/10.1186/s12890-016-0211-7
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