SENP3通过通过CTHTH的D-SUMOylation调节铁死来驱动腹腔大动脉动脉瘤的发展
Long Chen1, Zhaohua Cai1, Danrui Xiao1
1Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 28, 2025
概括
在巨细胞中,SENP3蛋白质通过破坏细胞胺-酶 (CTH) 的稳定性来促进腹腔大动脉动脉瘤 (AAA). 抑制SENP3或增强硫化为AAA提供了一个潜在的治疗策略.
科学领域:
- 血管生物学 血管生物学
- 炎症研究 炎症研究
- 疾病的分子机制.
背景情况:
- 腹腔大动脉瘤 (AAA) 是一种危险的炎症状况.
- 特定于SUMO2/3的蛋白酶SENP3与癌症的发展有关.
- 在AAA病变发生过程中SENP3的作用,特别是在巨细胞中,仍然不清楚.
研究的目的:
- 在AAA发育过程中研究巨细胞中SENP3的功能.
- 阐明SENP3影响AAA进展的分子机制.
主要方法:
- 在人类和小鼠AAA组织中分析SENP3蛋白表达.
- 生成髓特异性SENP3淘汰赛小鼠模型 (诱导AngII和CaCl2).
- 研究了SENP3,cystathionine gamma-Lyase (CTH) 和SUMOylation之间的相互作用.
- 评估了CTH抑制和硫化补充剂对AAA的影响.
主要成果:
- 在AAA标本中,SENP3蛋白表达显著升高.
- 骨髓细胞中SENP3的淘汰减弱了AAA的形成,并减少了巨细胞的透和炎症.
- SENP3 解SUMOylates 并促进 CTH 的降解,加剧铁和巨细胞的炎症.
- 抑制CTH可以逆转SENP3缺乏的保护作用,而补充H2S可以防止AAA.
结论:
- 通过SENP3介导的CTH脱SUMOylation是巨细胞铁和AAA发育的关键调节者.
- SENP3/CTH轴代表了腹腔大动脉动脉瘤的一个有前途的治疗点.
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