在内皮细胞中,METTL3调解了阿瑟罗流诱导的糖解
Guo-Jun Zhao1,2, So Yun Han2, Yajuan Li3,4
1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
概括
甲基转移酶3 (METTL3) 通过改变RNA修饰来驱动内皮细胞中以热流诱导的糖解. 作为SGLT2抑制剂的empagliflozin减轻了这一过程,为动脉样硬化提供了新的治疗途径.
科学领域:
- 血管生物学 血管生物学
- 代谢调节 代谢调节 代谢调节
- 史诗转录组学 史诗转录组学
背景情况:
- 甲基的流动通过增加糖解促进内皮细胞 (EC) 功能障碍和动脉样硬化启动.
- 甲基转移酶3 (METTL3) 是RNA N6-甲基氨酸 (m6A) 修改中的一个关键酶,影响细胞功能.
研究的目的:
- 调查METTL3在ECs中的阿瑟罗流诱导糖解中的作用.
- 阐明分子机制,将EC机械转导与在有机原条件下的代谢重编程联系起来.
主要方法:
- 在体外和体外的研究比较了EC的振荡式剪切应力 (OS) 和脉动式剪切应力 (PS).
- 对糖解相关酶mRNA (HK1,PFKFB3,GCKR) 的m6A修改进行分析.
- 对EC糖解和刺激拉曼散射 (SRS) 成像进行海马分析,用于葡萄糖的纳入.
主要成果:
- OS显著上调EC中的METTL3表达,增强HK1,PFKFB3和GCKRmRNAs的m6A修饰.
- 通过METTL3介导的m6A修饰改变了这些酶的表达,导致EC糖解和葡萄糖纳入脂质的增加.
- 恩帕格利弗洛辛 (SGLT2抑制剂) 治疗抑制METTL3表达并减轻OS诱导的糖解.
结论:
- METTL3在调节阿瑟罗流对EC糖解和代谢重编程的影响方面发挥着至关重要的作用.
- 向METTL3或使用SGLT2抑制剂,如empagliflozin,可以通过调节EC代谢来为动脉样硬化提供治疗策略.
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