调节肠道Wnt/β-catenin信号,从而导致肠道屏障破坏和全身炎症
Muskan Verma1, Manika Garg1, Aiysha Siddiq Khan1
1Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, Hamdard Nagar, New Delhi 110062, India.
Ecotoxicology and environmental safety
|April 19, 2024
概括
暴露于下调节了Wnt/β-catenin信号传输,损害了肠道. 激活这一途径反转了的作用.
科学领域:
- 胃肠病学 胃肠病学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 肠上皮质的完整性对于营养吸收和恒常性至关重要.
- 肠干细胞 (ISC) 调节了表皮细胞的快速循环.
- Wnt/β-catenin信号传递是肠道平衡的关键调节器,但其对环境因素的反应还没有得到充分研究.
研究的目的:
- 研究 (Cd) 暴露对肠道Wnt信号通路的影响.
- 阐明Wnt/β-catenin信号在Cd诱导的胃肠道毒性中的作用.
主要方法:
- 雄性BALB/c小鼠通过口腔 gavage 暴露于环境相关的Cd (0.98 mg/kg) 剂量.
- 采用了组织病理学,免疫组织化学,RT-PCR,西部斑点检测,ELISA,肠道透性测定和流细胞计.
- 在联合暴露实验中,使用LiCl (Wnt激活剂) 来调节Wnt信号.
主要成果:
- 亚慢性Cd暴露显著降低了标准Wnt信号通路的调节.
- 暴露于CD引起了广泛的小肠损伤,增加了肠道透性,并扭曲了免疫反应.
- 同时服用LiCl可逆转Cd诱导的胃肠道毒性,证实Wnt/β-catenin信号传递是主要的媒介.
结论:
- 主要通过降低Wnt/β-catenin信号轴的调节来产生胃肠道毒性.
- 这项研究强调了Wnt/β-catenin信号传递在调解环境污染物引起的肠损伤中的关键作用.
- 这些发现有助于我们更好地了解环境因素如何通过关键信号通路影响肠道健康.
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