转胺酶2通过IL-6介导的自细胞调节内皮细胞化
Bo Liu1, Zhiyuan Cai1, Yan Wang2
1Department of Cardiology, Zhengzhou Central Hospital, Zhengzhou University, Zhengzhou, Henan, China.
Frontiers in pharmacology
|December 10, 2024
概括
转胺酶2 (TG2) 通过激活NF-κB和IL-6信号来促进内皮细胞化,从而抑制自. 这种TG2介导的途径为动脉样硬化和血管化提供了新的见解.
科学领域:
- 心血管生物学 心血管生物学
- 细胞和分子医学是细胞和分子医学.
- 生物化学 生物化学
背景情况:
- 内皮细胞 (EC) 化是动脉样硬化和内脏化的关键标志物.
- ECs参与动脉动脉生成,并可能充当骨质生殖细胞,启动内脏化.
- 尽管已知它在细胞过程中的作用,但转谷氨酶2 (TG2) 介导的EC化的确切机制仍然不清楚.
研究的目的:
- 阐明TG2调节内皮细胞化的分子机制.
- 调查TG2在激活信号通路和调节EC中自的作用.
- 探索TG2,炎症和内皮细胞中化之间的联系.
主要方法:
- 使用siRNA和腺病毒载体进行TG2基因操纵 (过度表达/沉默).
- 对基因和蛋白质表达的分析 (RT-PCR,Western Blot),TG2活性 (5-BP检测) 和自水平 (LC3检测,电子显微镜).
- 在化条件下评估EC化 (Alizarin Red S染色,测定) 和IL-6水平 (ELISA).
主要成果:
- 化介质 (CM) 增加了TG2的活性和表达,激活了NF-κB通路,并诱导了IL-6自身隐性信号传递.
- IL-6激活了JAK2/STAT3通路,抑制了自和促进了EC化.
- 发现TG2与NF-κB成分形成复合物,将TG2与自抑制和EC化联系起来.
结论:
- TG2在通过NF-κB和IL-6/JAK2/STAT3信号通路促进内皮细胞化方面发挥着关键作用.
- 通过TG2信号抑制自促使内皮细胞化,并可能导致EndMT.
- 了解这种TG2介导的机制为动脉样硬化和血管化的病变产生提供了新的见解.
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