肝细胞中的脂质诱导颗粒可以缓解肝纤维化
Yunhui Li1, Ting Lei1, Wen Nie1
1National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai 200433, China.
Cell metabolism
|January 10, 2026
概括
研究人员在肝细胞中发现了由DDX49形成的脂质诱导颗粒 (LIG). 这些颗粒由脂质 (如阿拉基酸) 触发,通过抑制亲纤维基因转换来抑制肝纤维化.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 细胞内无膜器官对细胞功能和疾病过程至关重要.
- 死亡盒螺旋酶 (DDX) 蛋白质可以经历液-液相分离 (LLPS),形成无膜有机体.
- 识别新型器官及其功能是理解肝病的关键.
研究的目的:
- 在脂肪性肝细胞中识别新的无膜细胞器.
- 研究DDX家族成员在颗粒形成中的作用.
- 阐明这些颗粒如何影响肝纤维化的机制.
主要方法:
- 在脂肪性肝细胞中对DDX家族成员的查.
- 使用脂质诱导LLPS,特别是阿拉基酸 (AA) 代谢产物.
- 由DDX49.9形成的脂质诱导颗粒 (LIG) 的识别和表征.
- 对mRNA招募 (Timp2,YBX1) 和蛋白质翻译抑制的分析.
- 在人类MASLD肝脏样本中检查LIGs.
主要成果:
- 脂质,特别是AA代谢物,诱导了DDX49的LLPS,在肝细胞中形成LIG.
- 发现LIGs抑制了与代谢功能障碍相关的脂肪性肝病 (MASLD) 相关的纤维化.
- 在LIG中,招募了C5-甲基细胞因素 (m5C) 修饰的金属蛋白酶2 (Timp2) 和Y盒结合蛋白1 (YBX1) 的组织抑制剂mRNA.
- 招募抑制了Timp2mRNA的翻译,导致抑制的肝纤维化.
- 人类MASLD肝脏中存在LIGs,与纤维化进展相反相关.
结论:
- 鉴定出一种新型颗粒,LIG,由DDX49组装在脂肪性肝细胞中.
- 脂质代谢物诱导LIG的形成,对抗肝纤维化起着保护作用.
- 该机制涉及通过m5C修饰将亲纤维的mRNA转化隔离和抑制.
- LIGs代表了MASLD相关纤维化的潜在治疗标.
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