贫通过激活ER应激通过血栓素1-PERK通路诱导甲状腺损伤
Chang Shu1, Jie Li1, Suiyi Liu1
1State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, No.30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Chemico-biological interactions
|June 3, 2023
概括
贫 (DU) 通过降低血栓蛋白1 (TSP-1) 的调节和激活ER压力而导致甲状腺损伤. TSP-1可能是DU中毒的治疗目标.
科学领域:
- 毒理学 毒理学 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:
- 贫 (DU) 暴露对健康构成风险,但其对甲状腺功能的具体影响仍然不太清楚.
- 了解 DU 的甲状腺损伤机制对于开发有效的对策至关重要.
- 确定涉及DU毒性的关键分子通路对于有针对性的干预措施至关重要.
研究的目的:
- 在大鼠模型中研究 DU 对甲状腺结构和功能的影响.
- 为了阐明DU诱导的甲状腺损伤背后的分子机制.
- 确定潜在的治疗点,以减轻对甲状腺的DU毒性.
主要方法:
- 在老鼠中的急性DU暴露模型.
- 评估甲状腺结构,细胞亡和血清激素水平 (T4,FT4).
- 在体内和体外 (FRTL-5细胞) 进行基因表达分析 (TSP-1,PERK,CHOP,Caspase-3).
- 在细胞模型中利用TSP-1淘汰赛小鼠和TSP-1过度表达/抑制.
- 用4-Phenylbutyric酸 (4-PBA) 的干预来评估ER应激调制.
主要成果:
- 暴露于DU导致甲状腺积累,结构损伤,亡,并降低T4/FT4水平.
- 血栓素1 (TSP-1) 表达被DU显著下调,以剂量和时间依赖的方式.
- 与野生类型相比,TSP-1淘汰赛小鼠表现出严重的甲状腺损伤和激素水平降低.
- 在DU诱导的内等质网膜 (ER) 压力标志物 (PERK,CHOP) 和亡 (Caspase-3).
- 4-PBA治疗改善了DU诱导的甲状腺细胞损伤和降低激素水平.
- 确定TSP-1-PERK通路是DU诱导的甲状腺损伤的关键调解者.
结论:
- DU主要通过降低TSP-1的调节来诱导甲状腺损伤,从而通过PERK通路激活ER压力.
- TSP-1在甲状腺中起着保护性作用,防止DU的毒性.
- 准TSP-1-PERK通路为DU中毒提供了一个有前途的治疗策略.
- 进一步研究TSP-1作为DU诱导的甲状腺损伤的治疗点是有必要的.
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