刺之路负面调节的贫诱导的毒性
Xueying Xie1, Guoquan Fu1, Yuxin Liu1
1School of Life and Environmental Sciences, Shaoxing University, Shaoxing, Zhejiang, China.
Environmental toxicology
|March 28, 2024
概括
贫 (DU) 通过激活刺 (Hh) 途径而导致脏损伤. 抑制Gli2,一个关键的Hh效应因子,保护免受DU诱导的毒性,表明Gli2是潜在的治疗标.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 脏生理学 脏生理学
背景情况:
- 贫 (DU) 暴露带来了显著的放射性和化学毒性风险,脏是主要目标器官.
- 刺 (Hh) 信号通路与组织损伤反应有关,但其在 DU 诱导的毒性中的特定作用在很大程度上仍未被描述.
研究的目的:
- 调查Gli2在Hh通路中的关键转录因子Gli2在DU诱导的毒性病变的作用.
- 评估针对 Gli2 的治疗潜力,以减轻 DU 暴露引起的脏损伤.
主要方法:
- 使用条件淘汰赛小鼠模型 (CK19阳性管状上皮细胞特异性Gli2 KO) 暴露于DU.
- 分析了组织病理变化和组织中的Hh信号通路激活.
- 在使用Gant61 (Hh通路抑制剂) 和Gli2过度表达的HEK-293T细胞中评估DU诱导的细胞毒性.
主要成果:
- 暴露于DU导致显著的毒性,以Hh通路激活为特征.
- Gli2的遗传删除减弱了DU诱导的损伤和正常化的生化标志物.
- 用Gant61对Gli1/2进行药理抑制,通过抑制亡和活性氧物种 (ROS) 的形成,降低了DU细胞毒性.
- 过度表达Gli2加剧了DU诱导的细胞毒性,增加了细胞亡和ROS水平.
结论:
- Hh信号通路,特别是通过Gli2,在DU诱导的毒性中起着有害作用.
- 抑制Gli2显示出对暴露于DU的脏保护作用.
- 向Gli2代表了一种有前途的治疗策略,用于管理因贫污染造成的损伤.
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