The expression and pathophysiological role of osteopontin in Graves' disease.
The expression and pathophysiological role of osteopontin in Graves' disease.
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DOI：
10.1210/jc.2011-1339
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Lingyan Xu;Xinran Ma;Yan-ying Wang;Xiaoli Li;Yicheng Qi;B. Cui;Xiaoying Li;G. Ning;Shu Wang
中科院分区：
文献类型：
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作者：
Lingyan Xu;Xinran Ma;Yan-ying Wang;Xiaoli Li;Yicheng Qi;B. Cui;Xiaoying Li;G. Ning;Shu Wang
背景 格雷夫斯病 (GD) 是一种影响甲状腺的常见自身免疫性疾病。其发病机制与异常的促炎细胞因子的产生密切相关。骨桥蛋白（OPN）是一种具有多效性的细胞外基质蛋白，最近被认为是多种自身免疫性疾病中有效的炎症细胞因子。目的 本研究旨在通过比较初始 GD 患者和健康对照者的 OPN 水平，探讨 OPN 在 GD 中的病理生理学作用。方法 招募了 76 名符合初始 GD 标准的患者和 65 名健康对照者。测量 OPN 和其他临床 GD 诊断参数。此外，在人类受试者的外周血单核细胞中检查了几种 OPN 受体以及各种核因子 -κB (NF-κB) 下游靶基因的共表达。通过体外测定确定 OPN 对 NF-κB 激活的影响。结果我们首次证明 GD 患者血清中 OPN 水平升高。 OPN 水平与 GD 诊断的临床血清参数密切相关。 GD 患者外周血单核细胞中选择性 OPN 受体和炎症反应基因的共表达增强。此外，GD 患者的血清在体外激活 NF-κB 活性，而 OPN 单克隆抗体废除可显着抑制该活性。结论 这些数据表明血清 OPN 水平与 GD 之间存在临床相关性。 OPN 可以通过 NF-κB 激活以及随后炎症环境的变化影响 GD 的发展。 OPN 可以作为 GD 的新型生物标志物以及 GD 治疗的潜在靶点。
CONTEXT Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. Its pathogenesis is tightly involved with aberrant proinflammatory cytokine production. Osteopontin (OPN), an extracellular matrix protein of pleiotropic properties, has recently been recognized as a potent inflammatory cytokine in several autoimmune diseases. OBJECTIVE This study sought to explore the pathophysiological role of OPN in GD by comparing OPN levels in initial GD patients and healthy controls. METHODS Seventy-six patients who met criteria for initial GD and sixty-five healthy controls were recruited. OPN and other clinical GD diagnosis parameters were measured. In addition, the coexpression of several OPN receptors as well as various nuclear factor-κB (NF-κB) downstream target genes were examined in peripheral blood mononuclear cells from human subjects. The effect of OPN on NF-κB activation was determined by in vitro assays. RESULTS We demonstrated for the first time that the OPN levels are enhanced in serum from GD patients. OPN levels are strongly associated with clinical serum parameters for GD diagnosis. The coexpression of selective OPN receptors and inflammatory response genes was enhanced in peripheral blood mononuclear cells from GD patients. Furthermore, serum from GD patients activated NF-κB activity in vitro, which was significantly suppressed by OPN monoclonal antibody abrogation. CONCLUSION These data indicated a clinical correlation between serum OPN levels and GD. OPN could affect GD development through NF-κB activation and the subsequent changes in inflammatory milieu. OPN could serve as a novel biomarker for GD as well as a potential target for GD treatment.