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由YTHDF1介导的线粒体功能障碍和过敏性气道炎症是通过与β-catenin/TCF4信号交互引起的
Cancan Xie1, Junwen Huang2, Ying Chen2
1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangdong 510515, China; Department of Critical Care Medicine, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan 412007, China.
International immunopharmacology
|July 9, 2025
概括
N6-甲基氨酸 (m6A) 阅读器YTHDF1通过通过β-catenin/TCF4信号传递损害线粒体功能,加剧类固醇不敏感的喘. 在喘模型中抑制YTHDF1或β-catenin/TCF4信号减轻了呼吸道炎症和线粒体功能障碍.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 呼吸系统医学 呼吸系统医学
背景情况:
- N6-甲基氨酸 (m6A) 修饰和YTHDF1与过敏呼吸道炎症有关.
- m6A和YTHDF1在多二酸盐 (TDI) 诱导的类固醇不敏感喘中的作用尚不清楚.
- β-catenin信号传递对呼吸道炎症和喘中的线粒体功能至关重要.
研究的目的:
- 在TDI诱导的喘模型中研究β-catenin/TCF4信号与m6A依赖调节之间的相互作用.
- 探索YTHDF1在TDI诱导的类固醇不敏感喘中的作用.
主要方法:
- 已建立的小鼠喘模型使用TDI或室内灰尘虫 (HDM) 敏感化和挑战.
- 使用YTHDF1抑制剂 (Tegaserod),β-catenin/TCF4抑制剂 (LF3) 和线粒体稳定剂 (SS-31三酸盐).
- 利用了暴露于TDI的人类支气管上皮细胞和巨细胞进行体外研究.
主要成果:
- 在TDI诱导的喘模型 (TDI-AM) 中,YTHDF1被上调.
- 在TDI-AM和HDM模型中,低剂量Tegaserod缓解了呼吸道过敏反应,炎症,重塑和线粒体功能障碍.
- LF3抑制了呼吸道炎症,线粒体功能障碍和YTHDF1的表达,这表明YTHDF1与β-catenin/TCF4信号相互作用.
- SS-31三酸盐治疗减少了TDI诱导的呼吸道炎症和线粒体功能障碍.
结论:
- 通过与β-catenin/TCF4信号交互,YTHDF1调解线粒体功能障碍和过敏呼吸道炎症.
- 针对YTHDF1或β-catenin/TCF4信号可能为类固醇不敏感的喘提供治疗策略.
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