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格雷夫斯病患者外周血单个核细胞中差异 microRNA 的表达。

Differential microRNA expression in peripheral blood mononuclear cells from Graves' disease patients.

机构信息

Department of Endocrinology and Metabolism, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

出版信息

J Clin Endocrinol Metab. 2012 Jun;97(6):E968-72. doi: 10.1210/jc.2011-2982. Epub 2012 Mar 28.

DOI:10.1210/jc.2011-2982
PMID:22456620
Abstract

CONTEXT

Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, microRNA (miRNA) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease.

OBJECTIVE

This study sought to characterize the different miRNA expression in peripheral blood mononuclear cells (PBMC) from GD patients and healthy individuals and examine their direct responses to T(3) treatment.

METHODS

Forty-one patients who met criteria for initial GD, 13 GD patients in remission, and 35 healthy controls were recruited. Microarray was used to analyze the expression patterns of miRNA in PBMC obtained from initial GD patients and healthy controls. Three top-ranked miRNA were selected and validated by TaqMan-based real-time PCR in healthy controls, initial GD patients, and GD patients in remission. Furthermore, we cultured PBMC from healthy donors with or without T(3) treatment to examine direct effects of T(3) on selective miRNA.

RESULTS

There were sixteen miRNA expressed differently in PBMC from initial GD patients compared with normal subjects. Further analysis consistently showed that the expression of miR-154*, miR-376b, and miR-431* were suppressed in PBMC from initial GD patients. In addition, their expression levels were recovered in GD patients in remission. Meanwhile, T(3) treatment could directly inhibit the expression of these miRNA in cultured PBMC from healthy subjects.

CONCLUSIONS

The present work revealed that differentially expressed miRNA were associated with GD and T(3) exposure, which might serve as novel biomarkers of GD and potential targets for GD treatment.

摘要

背景

格雷夫斯病(GD)是一种常见的自身免疫性甲状腺疾病。作为基因表达调节剂的一类新物质,miRNA 已被报道在免疫功能以及自身免疫和自身免疫性疾病的发展中发挥重要作用。

目的

本研究旨在描述 GD 患者和健康个体外周血单个核细胞(PBMC)中不同 miRNA 的表达特征,并研究它们对 T3 治疗的直接反应。

方法

招募了 41 名符合初始 GD 标准的患者、13 名缓解期 GD 患者和 35 名健康对照者。采用微阵列分析初始 GD 患者和健康对照者 PBMC 中 miRNA 的表达模式。在健康对照者、初始 GD 患者和缓解期 GD 患者中,选择并验证了排名前三的 miRNA。此外,我们培养了健康供体的 PBMC,并用或不用 T3 处理,以研究 T3 对选择性 miRNA 的直接影响。

结果

与正常对照相比,初始 GD 患者 PBMC 中有十六种 miRNA 表达不同。进一步的分析一致表明,miR-154*、miR-376b 和 miR-431*在初始 GD 患者的 PBMC 中表达受到抑制。此外,在缓解期 GD 患者中,其表达水平得到恢复。同时,T3 处理可直接抑制健康供体培养的 PBMC 中这些 miRNA 的表达。

结论

本研究揭示了差异表达的 miRNA 与 GD 和 T3 暴露有关,它们可能作为 GD 的新型生物标志物和 GD 治疗的潜在靶点。

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