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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Human fibrocytes coexpress thyroglobulin and thyrotropin receptor
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Human fibrocytes coexpress thyroglobulin and thyrotropin receptor

机译：人纤维细胞共表达甲状腺球蛋白和促甲状腺激素受体

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摘要

Thyroglobulin (Tg) is the macromolecular precursor of thyroid hormones and is thought to be uniquely expressed by thyroid epithelial cells. Tg and the thyroid-stimulating hormone receptor (TSHR) are targets for autoantibody generation in the autoimmune disorder Graves disease (GD). Fully expressed GD is characterized by thyroid overactivity and orbital tissue inflammation and remodeling. This process is known as thyroid-associated oph-thalmopathy (TAO). Early reports suggested that in TAO, both Tg and TSHR become overexpressed in orbital tissues. Previously, we found that CD34~+ progenitor cells, known as fibrocytes, express functional TSHR, infiltrate the orbit, and comprise a large subset of orbital fibroblasts in TAO. We now report that fibrocytes also express Tg, which resolves as a 305-kDa protein on Western blots. It can be immunoprecipitated with anti-Tg Abs. Further, ~(125)iodine and [~(35)S]methionine are incorporated into Tg expressed by fibrocytes. De novo Tg synthesis is attenuated with a specific small interfering RNA targeting the protein. A fragment of the Tg gene promoter fused to a luciferase reporter exhibits substantial activity when transfected into fibrocytes. Unlike fibrocytes, GD orbital fibroblasts, which comprise a mixture of CD34~+ and CD34 cells, express much lower levels of Tg and TSHR. When sorted into pure CD34~+ and CD34~- subsets, Tg and TSHR mRNA levels become substantially higher in CD34~+ cells. These findings indicate that human fibrocytes express multiple "thyroid-specific" proteins, the levels of which are reduced after they infiltrate tissue. Our observations establish the basis for Tg accumulation in orbital GD.
机译：甲状腺球蛋白（Tg）是甲状腺激素的大分子前体，被认为由甲状腺上皮细胞唯一表达。 Tg和甲状腺刺激激素受体（TSHR）是自身免疫性疾病Graves病（GD）中自身抗体生成的目标。完全表达的GD的特征在于甲状腺过度活跃，眶组织发炎和重塑。这个过程被称为甲状腺相关性咽炎（TAO）。早期报道表明，在TAO中，Tg和TSHR在眼眶组织中均过表达。以前，我们发现CD34〜+祖细胞（称为纤维细胞）表达功能性TSHR，浸润轨道，并在TAO中包含很大的轨道成纤维细胞子集。现在，我们报告纤维细胞还表达Tg，在Western印迹上解析为305 kDa蛋白。可以用抗Tg Abs进行免疫沉淀。此外，将〜（125）碘和[〜（35）S]蛋氨酸掺入由纤维细胞表达的Tg中。从头开始的Tg合成被靶向该蛋白质的特定小干扰RNA削弱。与荧光素酶报道基因融合的Tg基因启动子片段在转染入纤维细胞时显示出实质性的活性。与纤维细胞不同，包含CD34 +和CD34细胞混合物的GD轨道成纤维细胞表达的Tg和TSHR含量要低得多。当分为纯CD34〜+和CD34〜-亚群时，Tg和TSHR mRNA水平在CD34〜+细胞中显着升高。这些发现表明，人纤维细胞表达多种“甲状腺特异性”蛋白，其在渗透组织后水平降低。我们的观察结果为轨道GD中Tg积累奠定了基础。

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    Roshini Fernando; Stephen Atkins; Nupur Raychaudhuri; Ying Lu; Bin Li; Raymond S. Douglas; Terry J. Smith;

  • 作者单位

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Ml 48105;

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Ml 48105;

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Ml 48105;

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Ml 48105;

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Ml 48105;

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Ml 48105;

    Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Ml 48105,Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Ml 48105;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    autoimmunity; monocyte; autoantigen;

    机译：自身免疫单核细胞自身抗原;

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