单胺通过mTOR/P70S6K通路在慢性结肠炎中抑制表皮层-介质细胞转换
Yuanfan Chen1,2,3, Jiaying Liu1, Shaowen Zhong1
1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Frontiers in pharmacology
|March 5, 2025
概括
来自传统中医药的单烯,通过阻断表皮层-介质细胞转换 (EMT) 来有效抑制慢性结肠炎中的肠纤维化. 这种作用与mTOR/P70S6K通路有关,为结肠炎相关纤维化提供了潜在的治疗策略.
科学领域:
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 慢性结肠炎通过表皮细胞-介质细胞过渡 (EMT) 构成肠道纤维化的风险.
- 来自Morinda officinalis的单素 (MON) 可能改善性结肠炎,但其机制和对纤维化的影响尚不清楚.
- 研究MON对慢性结肠炎EMT的影响对于了解其治疗潜力至关重要.
研究的目的:
- 在慢性结肠炎中研究单素对上皮层-介质细胞过渡 (EMT) 的作用.
- 阐明单胺在结肠炎相关纤维化中的作用的潜在分子机制.
主要方法:
- 一个慢性结肠炎的小鼠模型被使用德克斯硫酸盐 (DSS) 诱导.
- 在体内和体外使用TGF-β1诱导的IEC-6细胞评估了单烯对EMT的抑制作用.
- 分子对接,MD模拟,CETSA和DARTS测定确定了单质素的目标为mTOR.
主要成果:
- 单素显著改善了结肠损伤,并抑制了DSS诱导的大肠炎中的EMT标志物.
- 单胺直接向mTOR,抑制其酸化和下游信号在细胞和动物模型.
- 作为对单胺治疗的反应,观察到自活动的增加.
结论:
- 单胺在慢性结肠炎中有效抑制EMT,这表明它在预防肠道纤维化方面发挥了作用.
- 单素的治疗作用通过mTOR/P70S6K信号通路进行介导.
- 单烯为治疗慢性结肠炎相关肠纤维化提供了一个有前途的治疗药物.
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