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微小RNA在饮用水碘过量所致甲状腺功能亢进中的作用

The Role of miRNA in Hyperthyroidism Induced by Excessive Iodine in Drinking Water.

作者信息

Yang Zhihan, Dong Yishan, Wang Shuo, He Jing, Shen Zheng, Cheng Jin, Li Jinyu, Liu Qiaoling, Xu Ziqi, Sun Dianjun, Zhang Wei

机构信息

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.

Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province &, Ministry of Health, (23618504), Harbin, 150081, China.

出版信息

Biol Trace Elem Res. 2024 Sep 18. doi: 10.1007/s12011-024-04358-3.

Abstract

In recent years, iodine deficiency-related diseases have been effectively controlled; the prevalence of excessive iodine-induced thyroid diseases has increased, such as hyperthyroidism. However, there are still several controversial outcomes regarding the relationship between excessive iodine intakes and hyperthyroidism. MicroRNAs (miRNAs) extensively participate in the progression of thyroid diseases; nevertheless, the relationship and mechanism between iodine exposure and miRNAs have not been explored in hyperthyroidism patients. In this study, a total of 308 pairs of hyperthyroidism patients and healthy controls were enrolled in. Logistic regression analysis showed that level of water iodine >100 μg/L was an independent risk factor for hyperthyroidism. Compared with the healthy control, the serum thyroglobulin (Tg) content and levels of interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly elevated in hyperthyroidism patients. Further, high-throughput miRNA sequencing was applied to find crucial miRNAs involved in the occurrence of hyperthyroidism related to excessive water iodine. Based on the fold change and Q value, miR-144-3p, miR-204-5p, miR-346, miR-23b-5p, and miR-193b-3p were selected for validation by qRT-PCR. Our results showed that miR-346 and miR-204-5p in the case group were significantly lower than those of the control group, and the similar results found under the level of water iodine >300 μg/L. Nonetheless, no significant difference was found at 10-100 μg/L level of water iodine. Furthermore, the ROC curve indicated that miR-346 and miR-204-5p had the ability to diagnose hyperthyroidism patients. Taken together, excessive water iodine may decrease the expression of miR-346 and miR-204-5p, which mediate the elevation of Tg and cytokines, ultimately making contribution to the development of hyperthyroidism.

摘要

近年来,碘缺乏相关疾病已得到有效控制;碘过量所致甲状腺疾病的患病率有所上升,如甲状腺功能亢进症。然而,关于碘摄入量过多与甲状腺功能亢进症之间的关系仍存在一些有争议的结果。微小RNA(miRNA)广泛参与甲状腺疾病的进展;然而,碘暴露与miRNA之间的关系及机制在甲状腺功能亢进症患者中尚未得到探索。在本研究中,共纳入了308对甲状腺功能亢进症患者和健康对照。逻辑回归分析表明,水碘水平>100μg/L是甲状腺功能亢进症的独立危险因素。与健康对照相比,甲状腺功能亢进症患者血清甲状腺球蛋白(Tg)含量以及干扰素-γ(IFN-γ)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)水平显著升高。此外,应用高通量miRNA测序来寻找与水碘过量相关的甲状腺功能亢进症发生中涉及的关键miRNA。基于倍数变化和Q值,选择miR-144-3p、miR-204-5p、miR-346、miR-23b-5p和miR-193b-3p通过qRT-PCR进行验证。我们的结果显示,病例组中的miR-346和miR-204-5p显著低于对照组,在水碘水平>300μg/L时也发现了类似结果。然而,在水碘水平为10 - 100μg/L时未发现显著差异。此外,受试者工作特征曲线表明,miR-346和miR-204-5p具有诊断甲状腺功能亢进症患者的能力。综上所述,过量的水碘可能会降低miR-346和miR-204-5p的表达,这两种miRNA介导了Tg和细胞因子的升高,最终导致甲状腺功能亢进症的发生。

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