在NASH中由肝细胞线粒体功能障碍驱动的炎症信号传递
Melissa Myint1, Francesca Oppedisano2, Valeria De Giorgi3
1Sonata Therapeutics, Watertown, MA, USA.
Journal of translational medicine
|October 26, 2023
概括
非酒精性脂肪肝炎 (NASH) 中的线粒体功能障碍导致肝损伤. 损坏的线粒体会导致细胞死亡,激活免疫反应和纤维化,恶化这种常见的肝病.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 线粒体生物学 线粒体生物学
- 免疫学 免疫学 免疫学
背景情况:
- 非酒精性脂肪肝炎 (NASH) 涉及肝脏脂肪,炎症和纤维化.
- 它是一种非酒精性脂肪肝 (NAFL) 的攻击性形式,是一种普遍的慢性肝病.
- 肝细胞中的线粒体功能障碍是NASH病变发生的关键早期事件.
研究的目的:
- 调查线粒体功能受损在NASH中的作用.
- 了解脂毒性和氧化应激如何导致线粒体功能障碍.
- 阐明将线粒体功能障碍与NASH中的炎症和纤维化联系在一起的机制.
主要方法:
- 在脂毒条件下检查肝细胞中的线粒体功能.
- 评估了氧化应激对线粒体氧化酸化和ROS产生的影响.
- 研究了受压力肝细胞释放损伤相关分子模式 (DAMPs) 的情况.
- 分析了先天免疫和肝星细胞转分化的激活.
主要成果:
- 脂毒性和氧化应激会损害肝细胞中的线粒体功能.
- 线粒体功能障碍导致ROS产量增加和细胞死亡.
- 死亡的肝细胞释放DAMP,激活先天免疫细胞.
- 这一过程促进肝星细胞的激活,并驱动肝纤维化.
结论:
- 线粒体功能受损是NASH进展的关键驱动因素.
- 线粒体功能障碍在NASH中将脂毒性,氧化应激,炎症和纤维化联系在一起.
- 准线粒体通路可能为NASH提供治疗策略.
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