BMP9是内皮认同的关键参与者,其损失足以诱导动脉静脉形形
Agnes Desroches-Castan1, Dzenis Koca1, Hequn Liu1
1Laboratoire Biosanté U1292, Université Grenoble Alpes, Inserm, CEA, 17 avenue des Martyrs, 38054 Grenoble, France.
Cardiovascular research
|March 19, 2024
概括
骨形态遗传蛋白9 (BMP9) 损失导致血管异常和动脉静脉形 (AVM). 这项研究揭示了BMP9在维持血管平衡中的关键作用,以及它与遗传性出血端膜切开症 (HHT) 的联系.
科学领域:
- 血管生物学 血管生物学
- 分子机制的分子机制
- 遗传疾病 遗传性疾病
背景情况:
- 骨形态遗传蛋白9 (BMP9) 是ALK1和内林受体的配体,涉及遗传性出血性远程切除症 (HHT).
- 之前的研究表明,在129/Ola小鼠中,Bmp9缺乏导致肝纤维化和病变,原因是肝侧内皮细胞 (LSEC) 毛细化.
研究的目的:
- 阐明BMP9信号的下游分子机制.
- 描述BMP9在维持不同器官的血管平衡中的作用.
主要方法:
- 来自野生型 (WT) 和Bmp9-Knockout (Bmp9-KO) 小鼠的LSEC的RNA测序 (RNA-seq) 分析.
- 基因本体学分析以确定受影响的信号通路和细胞过程.
- 先进的成像技术,包括电子显微镜和免疫染色.
主要成果:
- 在Bmp9-KO LSEC中发现了2000多个差异表达的基因,表明BMP和Notch信号减少.
- 删除Bmp9导致LSEC毛细管的认同减少,细胞循环活性增加,以及质细胞的发育受损.
- Bmp9的丧失导致了多个器官的球毛细血管扩大,细胞变化和自发动脉静脉形 (AVM).
结论:
- 通过调节内皮细胞分化和细胞循环,BMP9对于维持血管静止至关重要.
- BMP9在血液中循环并系统地影响血管平衡,影响肝脏以外的器官.
- 缺乏BMP9足以引起自发的AVM,突出其在HT病原发生中的中心作用.
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