IL-10-TG/TPO-T4轴,bis (2-乙烯基) 四甲酸的目标对甲状腺功能失衡的影响
Yuese Yuan1, Yimeng Zhuang1, Yuan Cui1
1Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, PR China.
Toxicology
|December 22, 2023
概括
暴露于 bis ((2-乙) 四甲酸盐 (TBPH) 会增加甲状腺激素,并影响大鼠和人类细胞的基因表达. 这项研究确定IL-10-IL-10R-TG/TPO-T4轴是TBPH的关键途径.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 双二乙四甲酸盐 (TBPH) 是一种新型的制阻燃剂,可疑具有甲状腺破坏性.
- 有限的研究存在于TBPH的影响和与甲状腺功能相关的分子机制在体内和体外.
研究的目的:
- 研究TBPH对甲状腺功能的影响,并确定潜在的分子机制.
- 探索TBPH对大鼠和人类甲状腺细胞中的甲状腺特异性基因和细胞因子的影响.
主要方法:
- 雄性斯普拉格-道利大鼠和Nthy ori3-1人类甲状腺毛囊上皮细胞暴露于不同度的TBPH.
- 分析了甲状腺球蛋白 (TG),甲状腺过氧化酶 (TPO),化携运输体 (NIS) 和细胞因子 (IL-6,IL-10) 的基因和蛋白质表达.
- 用基因淘汰和抗体治疗来阐明分子途径.
主要成果:
- 在老鼠中,TBPH暴露显著增加了总甲状腺素 (TT4) 和自由甲状腺素 (FT4) 水平.
- 在大鼠甲状腺组织和人类细胞中,TBPH提高了TG,TPO,IL-6和IL-10的mRNA水平.
- 发现IL-10信号调节TBPH对TG和TPO表达的影响.
结论:
- 暴露于TBPH会破坏甲状腺激素稳态,并影响关键的甲状腺相关基因表达.
- IL-10-IL-10R-TG/TPO-T4轴被确定为TBPH甲状腺破坏作用的关键分子标.
- 这些发现突出了与TBPH暴露相关的潜在风险,并提供了对其毒理机制的见解.
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