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阿加罗特醇通过通过METTL14/FOXO3a通路调节自来缓解反流食道炎
Xi Chen1, Yeqing Yu2, Xiangxiang Xu3
1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; Department of Gastroenterology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
阿加罗特可以通过增强自来防止反流性食道炎 (RE). 它与METTL14结合,增加FOXO3a的表达,并激活保护通路.
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:
- 逆流性食道炎 (RE) 是一种具有显著炎症成分的疾病.
- 阿加罗特醇显示出强大的抗炎作用,有利于RE治疗.
- 自,由FOXO3a和METTL14调节,在减轻食道炎症方面发挥着至关重要的作用.
研究的目的:
- 在RE的背景下,研究阿加托特罗尔影响自的特定机制.
- 阐明FOXO3a和METTL14通路在阿加托特对RE的治疗作用中的作用.
主要方法:
- 建立了一种老鼠RE模型来评估阿加托特罗尔的疗效.
- 评估了炎症标志物,食道pH值和与自相关的蛋白质 (LC3B-II,p62).
- 分析了基因和蛋白质表达,m6A修饰 (MeRIP-qPCR) 和分子相互作用 (对接,MST).
- 该METTL14/FOXO3a途径进一步通过METTL14敲击模型进行了验证.
主要成果:
- 阿加罗特醇显著缓解了RE症状,减少了粘膜损伤和炎症,同时增加了食道pH值.
- 治疗上调自标志物 (LC3B-II) 和下调p62,表明自流量增强.
- 阿加罗特醇促进了FOXO3a mRNA的METTL14介导的m6A修饰,导致FOXO3a表达和自活性增加.
- 证实了阿加罗特和METTL14之间的直接结合;METTL14的敲击取消了阿加罗特对自的作用.
结论:
- 阿加罗特醇通过直接与METTL14结合,对RE产生保护作用.
- 这种相互作用增强了FOXO3a mRNA的m6A修饰,增加了FOXO3a的表达,并激活了保护性自途径.
- 这些发现突出了RE的新治疗机制,涉及METTL14介导的自的表观遗传调节.
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