阿尔法-托科菲瑞尔基通过AhR和Nrf2通路差异调节克劳丁,以增强肠道上皮质紧结屏障
Ashwinkumar Subramenium Ganapathy1, Kushal Saha1, Alexandra Wang1
1Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
维生素E的衍生品阿尔法-托科菲尔基 (TQ) 通过调节克劳丁蛋白来加强肠道屏障. 这种天然化合物通过增强紧密的结节来改善炎症性肠病症状.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肠表皮紧结 (TJ) 缺陷通过允许抗原透,有助于炎症性肠病 (IBD) 的病原发生.
- 恢复TJ完整性是IBD的潜在治疗策略.
研究的目的:
- 为了研究alpha-tocopherylquinone (TQ) 对肠道TJ屏障功能的影响.
- 阐明TQ对TJ蛋白的影响的分子机制及其在IBD中的治疗潜力.
主要方法:
- 使用Caco-2细胞单层的体外研究.
- 在体内研究,使用大肠炎的小鼠模型.
- 对手术切除的人体结肠的ex vivo分析.
- 研究基碳化合物受体 (AhR) 和核因子红色素2相关因子2 (Nrf2) 通路的激活.
- 基因删除研究以证实途径的参与.
主要成果:
- 通过增加克劳丁-3 (CLDN3) 和减少克劳丁-2 (CLDN2) 表达,TQ增强了肠道TJ屏障.
- 在多个模型中,TQ降低了结肠透性,改善了结肠炎症状.
- TQ 激活了 AhR 和 Nrf2 路径.
- 通过XRE通过TQ转录上调的CLDN3激活AhR.
- 通过TQ激活Nrf2,通过STAT3抑制抑制了CLDN2表达.
结论:
- 通过协调调节CLDN3和CLDN2.2,TQ可以增强肠道TJ屏障功能.
- 通过改善肠道屏障完整性,TQ证明了作为IBD治疗的无毒,天然存在的药物的治疗潜力.
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