USP29通过稳定ACSL5到K48双化来缓解MASLD的进展
Sha Hu1, Zhouxiang Wang1, Kun Zhu1
1Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, China.
Clinical and molecular hepatology
|October 2, 2024
概括
乌比基特异性蛋白酶29 (USP29) 通过稳定ACSL5来增强脂肪酸氧化,防止与代谢功能障碍相关的脂肪性肝病 (MASLD). 激活USP29为MASLD提供了一个潜在的治疗途径.
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
- 生物化学 生化学
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD) 是一种日益严重的健康问题,其特点是肝脏中脂肪的积累.
- 乌比基特异性蛋白酶29 (USP29) 在MASLD病变发生过程中的作用目前尚不清楚.
- USP29与其他肝脏疾病有关,如缺血-再输液损伤和肝细胞癌.
研究的目的:
- 研究USP29在MASLD进展中的作用和潜在的分子机制.
- 为了确定USP29表达是否在MASLD患者和动物模型中发生变化.
主要方法:
- 评估了来自MASLD患者和模型的人类和小鼠肝脏样本中的USP29表达.
- 使用高脂肪饮食和高脂肪/高胆固醇饮食诱导的MASLD的小鼠模型.
- 在培养肝细胞中使用棕酸和油酸处理来研究USP29的功能.
- 研究了USP29与ACSL5的相互作用及其对ACSL5降解的影响.
主要成果:
- 在MASLD患者和小鼠中,USP29蛋白水平显著下降.
- 缺乏USP29会加剧肝脏肥胖症,炎症和纤维化,而过度表达会改善这些情况.
- USP29通过二基化稳定了ACSL5,促进了脂肪酸β-氧化 (FAO).
- 针对MASLD的USP29的保护作用取决于ACSL5.5.
结论:
- USP29通过加强FAO通过ACSL5稳定作用,作为MASLD的新型负调节剂.
- USP29-ACSL5通路为治疗MASLD提供了一个有前途的治疗标.
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