通过使SMAD7脱和稳定,JOSD2抑制了血管新生素II诱导的血管改造
Si-Rui Shen1,2, Zhu-Qi Huang1,2,3, Yu-Die Yang1,2
1Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China.
Acta pharmacologica Sinica
|January 20, 2025
概括
双化酶JOSD2通过稳定SMAD7.7来防止血管新生素II诱导的血管改造. 缺少JOSD2会使重塑变得更糟,而过度表达则会扭转这种情况,突出其治疗潜力.
科学领域:
- 心血管生物学 心血管生物学
- 疾病的分子机制.
- 生物化学 生物化学
背景情况:
- 高血压的血管改造是由增加的血管素II (Ang II) 驱动的.
- 识别保护因素及其机制对于治疗开发至关重要.
研究的目的:
- 确定JOSD2作为抗Ang II诱导血管改造的保护因子.
- 在这个过程中阐明JOSD2的分子机制.
主要方法:
- 在Ang II挑战的小鼠血管组织中研究了JOSD2表达.
- 使用全身和VSMC特定的JOSD2淘汰/过度表达小鼠模型.
- 在JOSD2缺陷/过度表达的VSMC进行了体外研究.
- 进行RNA-seq和LC-MS/MS分析以确定分子通路和基质.
主要成果:
- 在Ang II挑战小鼠的VSMC中,JOSD2的调节升高.
- 在VSMC中,JOSD2缺陷加剧了Ang II诱导的血管改造,纤维化,增殖和迁移.
- 特定于VSMC的JOSD2过度表达逆转了这些效应.
- 而JOSD2则对SMAD7进行双化和稳定,SMAD7是TGFβ-SMAD通路的负调节者.
结论:
- JOSD2-SMAD7轴对于缓解Ang II诱导的血管改造至关重要.
- 通过稳定SMAD7,JOSD2作为保护因素,从而抑制VSMC功能障碍.
- JOSD2代表了高血压血管改造的潜在治疗标.
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