Title |
Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis
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Published in |
BMC Pulmonary Medicine, April 2016
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DOI | 10.1186/s12890-016-0211-7 |
Pubmed ID | |
Authors |
Domokos Bartis, Louise E. Crowley, Vijay K. D’Souza, Lee Borthwick, Andrew J. Fisher, Adam P. Croft, Judit E. Pongrácz, Richard Thompson, Gerald Langman, Christopher D. Buckley, David R. Thickett |
Abstract |
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). 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 3 | 75% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Practitioners (doctors, other healthcare professionals) | 2 | 50% |
Scientists | 1 | 25% |
Members of the public | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 53 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 7 | 13% |
Student > Bachelor | 6 | 11% |
Researcher | 6 | 11% |
Other | 4 | 8% |
Student > Postgraduate | 4 | 8% |
Other | 10 | 19% |
Unknown | 16 | 30% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 14 | 26% |
Biochemistry, Genetics and Molecular Biology | 6 | 11% |
Agricultural and Biological Sciences | 5 | 9% |
Immunology and Microbiology | 3 | 6% |
Nursing and Health Professions | 2 | 4% |
Other | 4 | 8% |
Unknown | 19 | 36% |