title: Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Respiratory Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom. d.bartis@outlook.com.|Department of Pharmacological Biotechnology, Szentágothai Research Centre, University of Pécs, 20 Ifjusag Utja, H-7624, Pécs, Hungary. d.bartis@outlook.com.
authors.forename: Domokos
authors.initials: D
authors.lastname: Bartis
authors.affiliation: Respiratory Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Louise E
authors.initials: LE
authors.lastname: Crowley
authors.affiliation: Respiratory Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: D'Souza
authors.affiliation: Fibrosis research group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Lee
authors.initials: L
authors.lastname: Borthwick
authors.affiliation: 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.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fisher
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Croft
authors.affiliation: Department of Pharmacological Biotechnology, Szentágothai Research Centre, University of Pécs, 20 Ifjusag Utja, H-7624, Pécs, Hungary.
authors.forename: Judit E
authors.initials: JE
authors.lastname: Pongrácz
authors.affiliation: Department of Heart & Lung Transplantation, University Hospital Foundation NHS trust Birmingham, Birmingham, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Thompson
authors.affiliation: Department of Pathology, Heart of England foundation NHS trust, Birmingham, United Kingdom.
authors.forename: Gerald
authors.initials: G
authors.lastname: Langman
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.affiliation: Respiratory Research Group, Centre for Translational Inflammation and Fibrosis Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: David R
authors.initials: DR
authors.lastname: Thickett
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015415:Biomarkers; C078203:CD248 protein, human; D012313:RNA
keywords: Biomarker; CD248; Endosialin; IPF; Idiopathic pulmonary fibrosis; TGF-beta