通过菌诱导的代谢重编程,AMPK维持肝星细胞的激活
Hanmin Wang1,2,3, Guanzhen Wang1,3, Tao Yin1,4,3
1State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Journal of molecular cell biology
|September 4, 2025
概括
通过促进肝星细胞 (HSC) 激活和线粒体功能,AMP激活蛋白激酶 (AMPK) 驱动肝纤维化. 抑制HSC中的AMPK可降低肝纤维化,突出显示AMPK- 线粒细胞的信号传递作为治疗点.
科学领域:
- 细胞生物学
- 代谢疾病
- 肝脏疾病
背景情况:
- 肝星细胞 (HSC) 的激活是肝纤维化的主要原因.
- 代谢重编程燃料激活HSCs进行矩阵合成.
- 在HSC激活和纤维化中AMP激活蛋白激酶 (AMPK) 的作用尚未完全理解.
研究的目的:
- 研究AMPK在HSC激活和肝纤维化进展中的作用.
- 阐明AMPK影响HSC代谢和功能的机制.
主要方法:
- 在人类和小鼠肝脏组织中检查AMPK酸化.
- 使用特定于HSC的AMPK淘汰小鼠模型 (CCl4和BDL诱导).
- 在不同AMPK活性和线粒细胞调节的HSC进行了体外研究.
主要成果:
- 在纤维性肝脏疾病中AMPK酸化升高.
- 特定于HSC的AMPK缺失显著降低了肝纤维化.
- 通过AMPK-ULK1/猛禽通路,AMPK促进了依赖于线粒体氧化化和线粒体化的HSC激活.
结论:
- 在肝细胞激活和肝纤维化中,AMPK起着至关重要的作用.
- 通过AMPK介导的线粒细胞衰变对于维护线粒体质量和激活HSC的能量供应至关重要.
- 向AMPK-mitophagy信号提供了一种新的肝纤维化治疗策略.
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