线粒体抗病毒信号蛋白通过ERK/TNFα/NFκβ途径增强MASLD的进展
Eva Nóvoa1,2, Natália da Silva Lima1, Maria J Gonzalez-Rellan1
1Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
Hepatology (Baltimore, Md.)
|May 18, 2024
概括
线粒体抗病毒信号蛋白 (MAVS) 通过增加脂质积累和炎症来驱动代谢功能障碍相关的脂肪性肝病 (MASLD). 在受损的肝细胞中抑制MAVS可以改善MASLD.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 线粒体抗病毒信号蛋白 (MAVS) 是对抗RNA病毒的先天免疫的关键,并与炎症性细胞因子分泌有关.
- 在代谢功能障碍相关的脂肪性肝病 (MASLD) 发病过程中,MAVS的作用仍然在很大程度上未被探索.
研究的目的:
- 调查MAVS在MASLD发展中的作用.
- 探索MAVS作为MASLD的潜在治疗点.
主要方法:
- 在被操纵p63表达的小鼠中的蛋白质组分析确定了MAVS作为下游目标.
- 在人类和动物MASLD模型中评估了MAVS表达.
- 对MAVS的遗传抑制在体外 (细胞系,初级肝细胞,球状细胞) 和体内 (小鼠) 进行.
- 分析了脂质含量,细胞因子水平 (TNFα) 和信号通路 (NFκβ,ERK).
主要成果:
- 在MASLD模型和患者的肝脏中,MAVS的表达是上调的.
- 在小鼠中,MAVS的遗传淘汰改善了饮食诱导的MASLD.
- 在体外,MAVS静音降低了脂质积累,而过度表达增加了它.
- MAVS抑制降低了TNFα和NFκβ,而ERK抑制阻断了MAVS诱导的TNFα激活.
- MAVS的O-GlcNAcylation对于其促炎和脂原性功能至关重要.
结论:
- 马维斯在肝脏肥胖症的发展中起着重要作用.
- 在受损肝细胞中准MAVS显示了改善MASLD的潜力.
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