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

BMC Pulmonary Medicine

Research Article

Richard Thompson¹  Gerald Langman²  Judit E. Pongrácz³  Lee Borthwick⁴  Andrew J. Fisher⁵  David R. Thickett⁶  Vijay K. D’Souza⁶  Louise E. Crowley⁶  Domokos Bartis⁷  Adam P. Croft⁸  Christopher D. Buckley⁸ 

[1] Department of Heart & Lung Transplantation, University Hospital Foundation NHS trust Birmingham, Birmingham, United Kingdom;Department of Pathology, Heart of England foundation NHS trust, Birmingham, United Kingdom;Department of Pharmacological Biotechnology, Szentágothai Research Centre, University of Pécs, 20 Ifjusag Utja, H-7624, Pécs, Hungary;Fibrosis research group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom;Fibrosis research group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom;Institute of Transplantation, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom;Respiratory Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom;Respiratory Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom;Department of Pharmacological Biotechnology, Szentágothai Research Centre, University of Pécs, 20 Ifjusag Utja, H-7624, Pécs, Hungary;Rheumatology Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom;

关键词: IPF;    Idiopathic pulmonary fibrosis;    TGF-beta;    CD248;    Endosialin;    Biomarker;   

DOI  :  10.1186/s12890-016-0211-7

 received in 2015-10-25, accepted in 2016-03-23,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCD248 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).MethodsCD248 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.ResultsIHC 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.ConclusionWe 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.

【 授权许可】

CC BY   
© Bartis et al. 2016