SMAD-INDEPENDENT TGF-BETA SIGNALING MECHANISMS IN ANGIOGENESIS

血管生成中独立于 SMAD 的 TGF-β 信号传导机制

• 批准号: 7609693
• 负责人: Calvin Pardee Hull Vary
• 金额: $ 18.81万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609693
• 关键词: ACVRL1 gene; Blood Vessels; Centers of Research Excellence; Computer Retrieval of Information on Scientific Projects Database; Data; Defect; ENG gene; Endoglin; Funding; Goals; Grant; Hereditary hemorrhagic telangiectasia; Human; Institution; Mediating; Molecular and Cellular Biology; Mus; Mutation; Pattern; Publishing; Research; Research Personnel; Resources; Signal Pathway; Signal Transduction; Source; TGF Beta Signaling Pathway; TGF beta type III receptor; Transforming Growth Factor beta Receptors; United States National Institutes of Health; angiogenesis; innovation; interest; primary pulmonary hypertension; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Vary has proposed the hypothesis that endoglin, a type-III TGF-beta receptor, is a BMPRII-mediated SMAD-independent effector of TGF-beta receptor ALK1 signaling that regulates angiogenesis. Human mutations in endoglin and ALK1 result in hereditary hemorrhagic telangiectasias 1 and 2 (HHT1, HHT2 respectively). In addition, human mutations in ALK1 and BMPRII are associated with primary pulmonary hypertension (PPH). In the mouse, ALK1 and endoglin have been shown to be required for angiogenesis. Taken together, these studies suggest that defects in endoglin (HHT1), ALK1 (HHT2), and BMPRII (PPH) disrupt a common signaling pathway. C. Vary's Published and preliminary data support this hypothesis and the two specific aims: 1) to identify BMPRII-mediated ALK1 signaling responses, and 2) to examine the consequences of endoglin and ALK1 expression on vascular patterning. This is a highly innovative project that is likely to resolve some of the paradoxes surrounding TGF-beta signaling pathways in the vasculature. These studies are an extension of C. Varys long-standing interest in the cell and molecular biology of endoglin function. The project is highly relevant to the aims and goals of this COBRE and is interactive with Projects 1 (Lindner) and 2 (Liaw). It is anticipated that rather strong collaborative interactions between these projects will continue to evolve.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 博士Vary提出了一种假说，即内皮糖蛋白（一种III型TGF-β受体）是调节血管生成的TGF-β受体ALK 1信号传导的BMPRII介导的SMAD非依赖性效应子。 内皮糖蛋白和ALK 1的人类突变导致遗传性出血性毛细血管扩张症1和2（分别为HHT 1、HHT 2）。 此外，ALK 1和BMPRII的人类突变与原发性肺动脉高压（PPH）相关。 在小鼠中，ALK 1和内皮糖蛋白已被证明是血管生成所需的。 总之，这些研究表明内皮糖蛋白（HHT 1），ALK 1（HHT 2）和BMPRII（PPH）的缺陷破坏了共同的信号传导途径。 C. Vary的已发表和初步数据支持这一假设和两个具体目标：1）鉴定BMPRII介导的ALK 1信号传导反应，2）检查内皮糖蛋白和ALK 1表达对血管模式的影响。这是一个高度创新的项目，可能会解决一些矛盾周围的TGF-β信号通路在血管系统。这些研究是C.变化他长期以来对内皮素功能的细胞和分子生物学感兴趣。该项目与COBRE的目的和目标高度相关，并与项目1（Lindner）和项目2（Liaw）互动。预计这些项目之间将继续发展相当强有力的协作互动。