通过METTL3介导的N6-甲基氨酸修饰有助于血管化
Long Li1, Quanyou Chai1, Chunling Guo2
1Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Hangzhou, China; Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Hangzhou, China; Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Journal of molecular and cellular cardiology
|April 13, 2025
概括
在慢性病 (CKD) 中,N6-adenosine-methyltransferase-like 3 (METTL3) 通过增加m6A修饰来促进血管化 (VC). 奎尔丁抑制METTL3,减轻了VC.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 心血管研究研究心血管研究
背景情况:
- 血管化 (VC) 是慢性病 (CKD) 中的一个显著的心血管并发症.
- 在VC中N6-甲基氨酸 (m6A) 修饰的作用和机制在很大程度上仍未被探索.
- 类似N6-adenosine-methyltransferase-3 (METTL3) 是一个关键的m6A编写酶.
研究的目的:
- 阐明METTL3在血管化 (VC) 中的作用.
- 调查METTL3在VC病变发生过程中的潜在分子机制.
- 确定针对VC的METTL3的潜在治疗策略.
主要方法:
- 在化血管光滑肌细胞 (VSMCs) 中对METTL3表达的生物信息分析.
- 在体外 (VSMCs) 和体内 (CKD小鼠模型) 实验验证METTL3在VC中的作用.
- 对m6A水平,沉积和信号通路的评估 (PTEN/AKT).
- RNA免疫沉降 (MeRIP) 试验以确认PTEN mRNA的m6A修饰.
- 分子对接和DARTS测试以确定奎尔素作为METTL3抑制剂.
主要成果:
- 在化VSMC和CKD小鼠的VC模型中,METTL3表达被上调.
- 过度表达METTL3增强了m6A水平并促进了化,而敲击抑制了这些效应.
- 通过 PTEN/AKT 途径通过诱导 PTEN mRNA 通过 m6A 修改降解,METTL3 促进了 VC.
- 奎尔赛丁被确定为METTL3的天然抑制剂,在体外和体内有效减轻VC.
结论:
- 通过m6A修饰,METTL3在血管化 (VC) 的病原发生中发挥着关键作用.
- 通过METTL3介导的PTENmRNA的m6A修饰有助于VC的发展.
- 在慢性病 (CKD) 患者中,METTL3代表了管理VC的有希望的治疗标.
- 奎尔丁通过抑制METTL3活性,显示出作为VC治疗剂的潜力.
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