调节光滑肌肉细胞表型的TWIST1域的功能分析
Danielle C M Dy1, Thiel Lehman2, Adrian Othon3
1Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Frontiers in cardiovascular medicine
|November 17, 2025
概括
TWIST1通过其域和二元化影响血管光滑肌肉细胞 (SMC) 的行为. 特定的TWIST1结构影响细胞迁移,增殖和信号通路,这些通路与动脉样硬化等血管疾病相关.
科学领域:
- 分子生物学分子生物学
- 心血管研究的心血管研究.
- 遗传学 是一个遗传学.
背景情况:
- TWIST1是一种转录因子,与发育和癌症有关.
- 全基因组关联研究将TWIST1与动脉样硬化和高血压等血管疾病联系起来.
- 在血管壁中TWIST1的精确分子作用尚未完全理解.
研究的目的:
- 调查TWIST1二元组合和特定域如何影响光滑肌肉细胞 (SMC) 表型.
- 阐明TWIST1在血管疾病中的作用背后的分子机制.
主要方法:
- 人类冠状动脉SMCs (HCASMCs) 用于表达TWIST1二元和缺乏特定域的变异.
- 进行了大量RNA测序,增殖试验和迁移试验.
- 来自人类内关节切除样本的单细胞RNA-seq数据被分析为疾病背景.
主要成果:
- TWIST1同质体促进了SMC的迁移和扩散,依赖于N端.
- 与E蛋白的异构化改变了转录组学,促进了Rho/ROCK信号传递和ECM产生,但不是迁移.
- TWIST1的C-终端删除诱导了显著的转录基因转移,表明了主导负效应,并防止了疾病中调制的SMC表型.
结论:
- TWIST1通过不同的域和二元组合影响SMC表型.
- TWIST1与关键信号通路 (Rho/ROCK,ECM) 相关,这些通路与血管疾病期间的SMC行为有关.
- 了解TWIST1的特定领域功能对于其在血管健康和疾病中的作用至关重要.
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