纤维细胞激活蛋白通过PLAUR/ITGB1-介导的促炎性巨细胞极化促进胸前大动脉解剖
Hongqiao Zhu1, Jianlie Wu2, Ziyi Xu1
1Department of Vascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 12, 2026
概括
纤维细胞激活蛋白 (FAP) 通过与巨细胞的非酶相互作用驱动胸前大动脉解剖 (TAD),而不是其酶活性. 准FAP/PLAUR/ITGB1/FAK通路为TAD提供了一个潜在的新疗法.
科学领域:
- 血管生物学 血管生物学
- 保护酶的功能 保护酶的功能
- 细胞信号传输 细胞信号传输
背景情况:
- 胸前动脉解剖 (TAD) 是一个危及生命的血管紧急情况,治疗选择有限.
- 纤维细胞激活蛋白 (FAP),一种参与组织重塑的蛋白酶,在TAD病原发生中的作用尚不清楚.
研究的目的:
- 调查FAP在TAD中的作用.
- 阐明FAP对TAD的贡献机制.
- 为了确定TAD的潜在治疗点.
主要方法:
- 在人类TAD标本和小鼠模型中评估FAP表达.
- 产生了全球性和纤维细胞特异性Fap淘汰小鼠.
- 利用RNA测序,药理抑制,SPR,co-IP和功能测试来研究FAP功能和相互作用.
主要成果:
- 在TAD病变中,纤维细胞衍生的FAP被上调.
- 脂肪酸删除减少了炎症,矩阵降解和TAD发生率.
- 通过非酶部位,FAP与巨细胞PLAUR相互作用,激活ITGB1 / FAK信号,并促进促炎性巨细胞表型,推动TAD进展. 酶抑制是无效的.
结论:
- FAP通过一种非酶性机制促进TAD,包括通过FAP/PLAUR/ITGB1/FAK轴的纤维细胞-巨细胞交叉.
- 这一途径代表了治疗TAD的潜在治疗策略.
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