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Lookup NU author(s): Dr Lee Borthwick,
Professor Andrew FisherORCiD,
Professor Christopher Buckley
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Bartis D, Crowley LE, D'Souza VK, Borthwick L, Fisher AJ, Croft AP, Pongracz JE, Thompson R, Langman G, Buckley CD, Thickett DR
Publication type: Article
Publication status: Published
Journal: BMC Pulmonary Medicine
Online publication date: 14/04/2016
Acceptance date: 23/03/2016
Date deposited: 08/07/2016
ISSN (electronic): 1471-2466
Publisher: BioMed Central Ltd
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