Deciphering the role of BMP9-BMP10 and YAP-TEAD signaling in vascular smooth muscle heterogeneity and pulmonary hypertension (A02)

解读 BMP9-BMP10 和 YAP-TEAD 信号在血管平滑肌异质性和肺动脉高压中的作用 (A02)

• 批准号: 314238338
• 金额: --
• 依托单位: Abteilung I: Entwicklung und Umbau des Herzens
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/314238338?language=en
• 关键词: Deciphering; role; BMP9; BMP10; YAP

BMP9 and BMP10 bind to the ALK1 receptor, which is linked to pulmonary hypertension (PH). We found that genetic inactivation of BMP9/10 in mice causes dramatic changes in vascular tone and diminution of vascular smooth muscle cells (VSMC), protecting mice from hypoxia-induced PH. These effects are mediated by vascular bed-specific expression of Alk receptors in VSMC. We will elucidate the impact of the BMP9/BMP10/Alk1 axis on reverse remodeling of pulmonary arteries, analyze the meaning of heterogeneous Alk-receptor expression in VSMCs, explore the cross-talk between Alk1/Smad1/5/8 and YAP-TEAD signaling and elucidate the impact of BMP9/10 dependent differential splicing in VSMCs.

BMP 9和BMP 10与ALK 1受体结合，ALK 1受体与肺动脉高压（PH）有关。我们发现，在小鼠中的BMP 9/10的基因失活引起血管张力和血管平滑肌细胞（VSMC）的减少，保护小鼠从缺氧诱导的PH的显着变化。这些影响是由血管床特异性表达的ALK受体在VSMC介导的。我们将阐明BMP 9/BMP 10/Alk 1轴在肺动脉逆重构中的作用，分析VSMCs中Alk受体异质性表达的意义，探讨Alk 1/Smad 1/5/8和YAP-TEAD信号之间的相互作用，并阐明BMP 9/10依赖的差异剪接在VSMCs中的作用。