内分泌素作为血管内皮细胞中的BMP9共受体:原域位移和TGFBRII招募
Jingxu Guo1, Karolina Kostrzyńska1, Ioannis Kamzolas2,3
1The Victor Phillip Dahdaleh Heart & Lung Research Institute, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Nature communications
|December 31, 2025
概括
内分泌蛋白 (ENG) 作为共受体,促进BMP9/BMP10联体的捕获和TGF-β通路的信号传递. 这项研究澄清了 ENG.
科学领域:
- 分子生物学分子生物学
- 血管生物学 血管生物学
- 生物化学 生物化学
背景情况:
- 内分泌蛋白 (ENG) 是一种跨膜蛋白,对内皮细胞 (EC) 功能至关重要.
- ENG与诸如肺动脉高血压 (PAH) 等心血管疾病有关.
- ENG功能的精确分子机制,特别是它在TGF-β和BMP信号传递中的作用,仍然不清楚.
研究的目的:
- 阐明内分泌蛋白 (ENG) 的双重共受体功能.
- 澄清NG在TGF-β信号传递中的作用及其与BMP9和BMP10的高亲和结合之间的关系.
- 调查针对血管疾病的ENG治疗潜力.
主要方法:
- 研究了 ENG 与 BMP9 和 BMP10 的相互作用.
- 分析了ENG在招募TGFBRII到BMP9信号综合体中的作用.
- 在人类肺组织和PAH患者中,NG,NOG和ADAMTSL2的相关表达水平.
主要成果:
- ENG从BMP9和BMP10中取代产域,从而增强连接物捕获.
- ENG将TGFBRII招募到BMP9信号综合体中,将TGF-β和BMP9通路连接起来.
- NOG和ADAMTSL2被确定为依赖NG的BMP9点基因,在PAH中表达减少.
结论:
- 内分泌蛋白 (ENG) 作为一个关键的共同受体,介导BMP9/BMP10捕获和TGF-β通路信号传递.
- 这些发现澄清了ENG的复杂生物学及其参与TGF-β和BMP9通路.
- 了解 ENG 的机制为治疗血管疾病 (如 PAH) 的治疗策略提供了洞察力.
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