通过促进AKT的甲基化来缓解肠道屏障功能障碍
Chuanjiang Cai1, Yining Zheng1, Bo Sun1
1College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|July 11, 2025
概括
激活AKT信号,通过增强甲基化来改善肠道屏障功能. 限制histidine可能有利于炎症性肠道疾病,如克罗恩氏病和性结肠炎.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 对于肠道屏障的完整性至关重要,并用于预防肠道疾病.
- 对肠道屏障的调节作用的确切机制在很大程度上是未知的.
研究的目的:
- 为了识别和描述AKT的反应激活.
- 为了阐明可以缓解肠道屏障功能障碍的分子途径.
- 探索调节和胺摄入量用于肠道疾病的治疗潜力.
主要方法:
- 通过ZNG1-METAP1复合体,研究了诱导的细胞内SAM产生.
- 在特定残留物 (R391,R15) 中进行特征性PRMT5-介导的AKT甲基化,形成AKTSDMA.
- 评估了AKT转位,mTORC2相互作用以及对细胞增殖和肠道屏障功能的下游影响.
- 研究了希斯蒂丁对介导通路的对抗作用.
主要成果:
- 通过激活ZNG1-METAP1复合体来增加细胞内SAM的产生.
- 促进PRMT5介导的AKT甲基化 (形成AKTSDMA),促进其转位和与mTORC2相互作用,导致AKT激活和细胞增殖.
- 伊斯蒂丁通过结合来对抗的作用,抑制AKT激活和改善肠道屏障.
- ZNG1-METAP1-PRMT5-AKTSDMA通路调解对肠道屏障功能的有益作用.
结论:
- 通过ZNG1-METAP1-PRMT5-AKTSDMA路径激活AKT信号,从而缓解肠道屏障功能障碍.
- 准这种途径并可能限制希斯蒂丁摄入量为炎症性肠道疾病提供了一种新的治疗策略,包括克罗恩病和性结肠炎.
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