EMC10以异构体特定的方式调节肝脏ER应激和肥胖症
Kuangyang Chen1, Yahao Wang2, Jia Yang2
1Department of Endocrinology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Department of Endocrinology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Journal of hepatology
|April 10, 2024
概括
细胞内网膜蛋白质复合体子单元10 (EMC10) 具有两种异构体,在代谢功能障碍相关的脂肪性肝病 (MASLD) 中具有相反的作用. 向分泌的异型 (scEMC10) 为MASLD提供了一个潜在的治疗策略.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 膜蛋白复合体10 (EMC10) 亚单元10 (EMC10) 与肥胖有关.
- 存在两个EMC10异型,分泌 (scEMC10) 和膜结合 (mEMC10).
- 研究了它们在代谢功能障碍相关的脂肪性肝病 (MASLD) 中的作用.
研究的目的:
- 调查scEMC10和mEMC10在MASLD病变发生过程中的不同作用.
- 探索在MASLD中准scEMC10的治疗潜力.
- 检查EMC10异型与人类MASLD的相关性.
主要方法:
- 利用稳定性小鼠模型和HepG2细胞来研究EMC10对肝脏PERK-eIF2α-ATF4信号传递和稳定性的影响.
- 评估了scEMC10中和抗体的治疗疗效.
- 在人类MASLD队列中分析了血清scEMC10和肝脏mEMC10水平.
主要成果:
- scEMC10促进,而mEMC10抑制,肝脏ER压力和脂肪.
- EMC10基因淘汰变得更糟,而mEMC10过度表达改善,小鼠肝硬化.
- 中和scEMC10可以预防饮食引起的肝硬化.
- 血清scEMC10升高和肝脏mEMC10降低与人类的MASLD严重程度相关.
结论:
- 在MASLD中,EMC10表现出异型特异性的功能.
- mEMC10对肝脏ER压力和脂肪酸有保护作用.
- scEMC10作为MASLD发展的驱动力.
- scEMC10是MASLD的一个有前途的治疗点.
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