肝细胞EVs通过SIRT1/SREBP-1c/PGC-1α信号在初级小牛肝细胞中调节脂质代谢
Daoliang Zhang1,2, Jishun Tang3, Leihong Liu1
1College of Veterinary Medicine, Anhui Agricultural University, Hefei 230061, China.
International journal of molecular sciences
|October 16, 2025
概括
来自非基因性小牛的细胞外囊泡 (EVs) 可以通过调节SIRT1/SREBP-1c/PGC-1α信号来缓解基因性小牛的肝脂乱. 相反,来自性小牛的EV会使这些脂质代谢问题恶化.
科学领域:
- 分子生物学分子生物学
- 动物科学动物科学
- 生物化学 生物化学
背景情况:
- SIRT1-SREBP-1c/PGC-1α信号通路对于调节非化脂肪酸 (NEFAs) 和肝脂代谢至关重要,特别是在性小牛犊中.
- 来自小牛肝细胞的细胞外囊 (EV) 越来越多地被认为是它们在细胞间通信中的作用和对肝功能潜在的影响.
- 了解肝细胞衍生的EVs在脂质新陈代谢中的作用,对于解决性小牛肝脂质疾病至关重要.
研究的目的:
- 在实验室中研究来自非基因性 (NK) 和基因性 (CK) 牛犊肝细胞的细胞外囊泡 (EV) 对脂质代谢的影响.
- 阐明SIRT1/SREBP-1c/PGC-1α信号通路在肝细胞衍生的EVs对肝脂代谢的作用中的参与.
- 探索NK衍生的EVs作为治疗策略的潜力,以缓解性小牛的脂质代谢障碍.
主要方法:
- 在实验室中建立非症 (NK,0 mM NEFA) 和临床症 (CK,2.4 mM NEFA) 的小牛肝细胞模型.
- 从NK和CK肝细胞的培养超水体中提取EVs.
- 用NK衍生和CK衍生EV治疗正常和NEFA挑战的肝细胞模型,然后对SIRT1/SREBP-1c/PGC-1α信号通路基因和蛋白质表达进行分析.
主要成果:
- 从NK衍生的EV显著抑制了SREBP-1c的表达,同时在肝细胞中上调SIRT1和PGC-1α的表达 (p <0.05).
- 在正常肝细胞中,CK衍生的EV诱导了脂质代谢障碍,并加剧了NEFA诱导的脂质失衡 (p <0.05).
- 过度表达SIRT1证实了EVs通过SIRT1/SREBP-1c/PGC-1α通路调节肝细胞脂质代谢的作用.
结论:
- 从NK衍生的EVs通过调节SIRT1/SREBP-1c/PGC-1α信号通路来缓解性小牛的肝脂代谢障碍.
- 由CK衍生的EV会加剧脂质代谢障碍,这表明它在性状况中起着有害的作用.
- 从NK衍生出来的EVs高调脂质氧化和低调脂质合成,表明它们作为治疗性小牛肝脂质障碍的生物提取物的潜力.
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