NINJ1通过阻断TLR4-ANXA2相互作用和增强巨细胞透来促进腹腔大动脉动脉瘤的形成
Zhaoyu Wu1,2, Zhijue Xu1,3, Hongji Pu1
1Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|June 26, 2024
概括
神经损伤诱导蛋白1 (NINJ1) 通过增加巨细胞透和炎症来促进腹腔大动脉动脉瘤 (AAA). 在巨细胞中抑制NINJ1会减少AAA的发展,这表明NINJ1是AAA的潜在治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 炎症研究 炎症研究
- 分子医学是分子医学.
背景情况:
- 腹腔大动脉动脉瘤 (AAA) 的发病包括慢性大动脉炎症.
- 神经损伤诱导蛋白1 (NINJ1) 是炎症的关键调节者.
- 对于NINJ1在AAA发展中的作用尚不清楚.
研究的目的:
- 研究NINJ1在腹腔大动脉动脉瘤形成中的作用.
- 阐明NINJ1影响AAA病变的分子机制.
主要方法:
- 在人类和小鼠AAA病变中分析NINJ1表达.
- 产生和使用宏特定的NINJ1淘汰小鼠 (Ninj1flox/floxLyz2-Cre 在 ApoE-/- 背景).
- 关于巨细胞行为和炎症反应的体外研究.
- 大量RNA测序和蛋白质-蛋白质相互作用分析.
主要成果:
- 在人类和Ang II诱导的小鼠AAA中,NINJ1的表达被上调.
- 巨细胞NINJ1缺陷显著抑制AAA的形成,并减少巨细胞的透.
- 在体外,NINJ1抑制限制了巨细胞的粘附,迁移和促炎反应.
- 通过与ANXA2.2相互作用,NINJ1通过TLR4/NF-κB/CCR2通路调节巨细胞透.
结论:
- NINJ1通过增强巨细胞透和炎症反应来促进AAA的形成.
- 在巨细胞中准NINJ1为腹腔大动脉瘤提供了潜在的治疗策略.
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