Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis.
Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis.
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DOI：
10.1186/s12890-016-0211-7
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发表时间：
2016-04-14
影响因子：
3.1
通讯作者：
Thickett DR
中科院分区：
文献类型：
--
作者：
Bartis D;Crowley LE;D'Souza VK;Borthwick L;Fisher AJ;Croft AP;Pongrácz JE;Thompson R;Langman G;Buckley CD;Thickett DR
CD 248或内皮唾液酸蛋白是在基质细胞中表达的与细胞外基质（ECM）组分结合的跨膜分子。它以前已经涉及肾纤维化，类风湿性关节炎以及肿瘤-基质相互作用。本研究探讨了CD 248在特发性肺纤维化（IPF）纤维化疾病发病机制中的作用。对22例IPF患者的肺样本进行CD 248定量免疫组织化学（IHC），并测定其在培养的肺成纤维细胞和上皮细胞中的表达。评价了CD 248沉默对成纤维细胞增殖和肌成纤维细胞分化的影响。免疫组化显示，CD 248在正常肺结构（如胸膜和外膜）的间充质细胞中有强表达，但在上皮中无表达。纤维化区域显示出比未受影响的肺组织明显更强的染色。CD 248染色程度与肺功能指标FEV 1、FVC、TLC、TLCO呈显著负相关（r 2> 0.35，p <0.01）。与正常肺成纤维细胞相比，IPF衍生的肺成纤维细胞中的CD 248蛋白水平显著更高（p <0.01），并且CD 248沉默显著降低肺成纤维细胞的增殖，但不影响肌成纤维细胞分化。我们的结论是，CD 248过表达可能参与了IPF的发病机制，它有可能作为疾病严重程度的标志物。鉴于CD 248配体是I型、IV型胶原和纤连蛋白，我们假设CD 248信号传导代表了一种新的基质-成纤维细胞相互作用，可能是IPF的潜在治疗靶点。本文的在线版本（doi：10.1186/s12890-016-0211-7）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s12890-016-0211-7) contains supplementary material, which is available to authorized users.