拉斯相关蛋白2限制了血管光滑肌细胞表型切换和腹腔大动脉动脉瘤发展
Shanshan Luo1, Jiyu Chen1, Ke Zhong1
1Key Laboratory of Drug Targets and Translational Medicine for Cardio-cerebrovascular Diseases, Nanjing Medical University, Nanjing, China.
Nature communications
|October 28, 2025
概括
与RAS相关的C3毒素基质2 (RRAS2) 缺乏会加剧腹腔大动脉动脉瘤 (AAA) 的发展. 恢复RRAS2水平可能为AAA提供治疗策略.
科学领域:
- 血管生物学 血管生物学
- 遗传学 是一个遗传学.
- 分子医学是分子医学.
背景情况:
- 腹腔大动脉动脉瘤 (AAA) 破裂是死亡的主要原因.
- 在AAA病变发生过程中RRAS2的作用在很大程度上是未知的.
- RRAS2突变与努南综合征有关.
研究的目的:
- 研究RRAS2在AAA中的作用.
- 阐明RRAS2在血管光滑肌细胞 (VSMC) 中的功能背后的分子机制.
主要方法:
- 来自AAA患者和小鼠的RNA-seq数据的综合分析.
- 生成特定于SMCs的Rras2淘汰和过度表达的小鼠模型.
- ангиотензин II (Ang II) 和猪胰腺弹性酶诱导的AAA模型.
- 研究MEG3,ELAVL1和RRAS2.2之间的相互作用.
- 对GTF2-I酸化,核转位和转录活动的分析.
主要成果:
- 在AAA中,RRAS2 mRNA和蛋白质水平下降.
- 特定于SMC的Rras2淘汰赛小鼠对AAA诱导的脆弱性增加.
- 过度表达RRAS2可以抑制AAA的进展.
- 通过抑制其通过ELAVL1.1降解,MEG3稳定了RRAS2mRNA.
- 失去R-Ras2会损害GTF2-I的活性,减少收缩基因表达.
结论:
- 在维护VSMC平衡中,RRAS2起着至关重要的保护作用.
- RRAS2是预防AAA进展的潜在治疗点.
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