脂肪酸的合成和氧化通过通过乙化调节SMAD3核定位,调节人体内皮的分化
Ying Yi1, Xianchun Lan1, Yinglei Li1
1Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Developmental cell
|July 29, 2023
概括
脂肪酸代谢调节人类内皮的分化. 增强脂肪酸氧化和抑制合成,通过增加乙-CoA用于SMAD3乙化,促进干细胞分化.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 干细胞分化的过程
- 代谢调节 代谢调节 代谢调节
背景情况:
- 代谢重塑是细胞分化的关键早期事件.
- 脂肪酸代谢在人类干细胞分化成最终内皮中的作用尚未完全理解.
研究的目的:
- 研究脂肪酸代谢在人类胚胎干细胞分化成最终内皮中的作用.
- 阐明脂肪酸代谢调节这种分化过程的机制.
主要方法:
- 利用人类胚胎干细胞进行分化研究.
- 研究脂肪酸合成和氧化途径的变化.
- 检查了AMP激活蛋白激酶 (AMPK) 和乙烯基-CoA核糖酶 (ACC) 的作用.
- 评估了代谢抑制剂和激动剂对差异化的影响.
主要成果:
- 脂肪酸β-氧化增强,而脂质生成在分化过程中减少.
- 通过AMPK介导的ACC酸化有助于减少脂质生成.
- 抑制脂肪酸合成或激活AMPK促进了内皮分化.
- 脂肪酸氧化阻塞损害了分化.
- 减少脂肪酸合成和增加氧化导致细胞内乙-CoA的积累.
- 乙-CoA的积累促进了SMAD3的乙化和核定位,推动了分化.
结论:
- 脂肪酸代谢的转变,有利于氧化而不是合成,对于最终的内皮分化至关重要.
- 由脂肪酸代谢调节的细胞内乙-CoA积累是关键的信号机制.
- 脂肪酸代谢在调节人类内皮与胚胎干细胞分化方面发挥着指导性的作用.
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