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

Domokos Bartis,David R Thickett,Andrew J Fisher,Christopher D Buckley,Lee Borthwick,Adam P Croft,Judit E Pongrácz,Vijay K D’Souza,Louise E Crowley,Richard Thompson,Gerald Langman

doi:10.1186/s12890-016-0211-7

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0211-7) contains supplementary material, which is available to authorized users.

Highlights

CD248 or Endosialin is a transmembrane molecule expressed in stromal cells binding to extracellular matrix (ECM) components
CD248 immunohistochemistry staining pattern on fibrotic lung CD248 expression was compared in lung samples from patients with Idiopathic Pulmonary Fibrosis (IPF) who underwent either video assisted thoracoscopic (VATS) biopsy or lung transplantation
There was a visible difference between CD248 expression patterns in lung samples with mild or moderate fibrosis and severe fibrosis (Fig. 1a and b, respectively.) Fibroblastic foci generally stained less intensive or not at all for CD248 in comparison to the surrounding fibrosis

Summary

Introduction

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. Effector cells are activated fibroblasts or myofibroblasts residing in large numbers in fibroblastic foci, a characteristic feature of usual interstitial pneumonia. These alpha smooth muscle actin (α-SMA)-expressing cells secrete. Bartis et al BMC Pulmonary Medicine (2016) 16:51 large amounts of collagen and other extracellular matrix (ECM) components and are considered to be responsible for pathological tissue remodelling [10]. The degree of involvement of EMT in IPF pathogenesis— the number of fibroblasts and myofibroblasts derived from transdifferentiated epithelial cells—is currently debated [7, 11, 12]

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Conclusion