肝脏机制作为一种天然的抗乙肝B病毒机制发出信号
Jianyu Ye1,2, Fahong Li1,3, Ting Hua1,2
1Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Huashan Hospital, Shanghai Medical College Fudan University, Shanghai, China.
Nature communications
|September 27, 2024
概括
乙型肝炎病毒 (HBV) 复制被肝脏矩阵硬性抑制,从而激活YAP. 激活YAP和向YAP的药物显示出控制HBV感染的潜力.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 病毒学 病毒学
- 机械生物学 机械生物学
背景情况:
- 对于乙型肝炎病毒 (HBV) 感染的自然控制机制的理解尚不完全.
- 肝脏的机械微环境越来越多地被认为是其在生理稳态和疾病发病过程中的作用.
研究的目的:
- 为了研究物理矩阵线索对HBV复制的影响.
- 探索YAP机械信号在控制HBV感染中的作用.
主要方法:
- 使用初级肝细胞培养系统来评估矩阵刚度对HBV复制的影响.
- 使用小分子激动剂诱导YAP激活.
- 对活跃HBV感染患者的肝脏组织进行了单细胞分析.
- 在雄性小鼠模型中评估了HBV控制.
主要成果:
- 高矩阵刚度显著抑制了HBV复制,并在肝细胞中激活了YAP.
- YAP激活抑制了HBV转录和抗原表达,YAP诱导的基因表现出抗HBV效应.
- 在患者肝脏组织中观察到YAP签名激活和HBV转录水平之间存在显著的负相关性.
- 在小鼠模型中,YAP激动剂的内注射有效控制了HBV.
结论:
- 由YAP介导的肝细胞的机械微环境在清除HBV感染中起着至关重要的作用.
- 针对YAP机械信号,为HBV感染和抗病毒开发提供了一种新的治疗策略.
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