向DRP1Ser637酸化通过线粒体保护缓解酸胆盐诱导的NF-κB激活
Yanqing Yang1, Zhenghui Zhu1, Xinyan Li1
1Department of Gastroenterology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, Jiangsu, China.
Journal of gastroenterology and hepatology
|July 31, 2025
概括
在GERD中,胆酸会通过DRP1酸化引起线粒体碎片化和炎症. 针对这种途径可以通过恢复线粒体功能来治疗GERD.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 线粒体动力学在胃食道逆流性疾病 (GERD) 中的作用尚不清楚.
- 在GERD病变发生过程中研究胆酸诱导的线粒体功能障碍.
研究的目的:
- 阐明GERD中线粒体功能障碍的机制.
- 为了确定与GERD相关的粘膜炎症的治疗点.
主要方法:
- 从GERD患者和对照对食道活检的RNA测序.
- 在体外研究中,使用用酸性胆盐 (ABS) 治疗的人类食道上皮细胞 (HEEC).
- 分析线粒体形态,功能和DRP1修饰;采用DRP1淘汰和药理抑制.
主要成果:
- GERD患者表现出丰富的线粒体分裂和NF-κB通路.
- 在HEEC中,ABS暴露诱导了DRP1 Ser637酸化,线粒体碎片化和mtROS产生.
- DRP1抑制 (H-89) 恢复了线粒体功能并减少了炎症,这种效应取决于DRP1酸化.
结论:
- 由ABS诱导的DRP1 Ser637酸化驱动了GERD中的线粒体碎片化和炎症.
- 矛盾的是,由DRP1介导的线粒体裂变通过质量控制来限制粘膜损伤.
- 向DRP1酸化为GERD提供了一个潜在的治疗策略.
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