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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Vary博士提出了以下假设：IS-III TGF-BETA受体Endoglin是BMPRII介导的TGF-BETA受体ALK1信号的BMPRII介导的SMAD独立效应子，可调节血管生成。 内源和ALK1中的人类突变导致遗传性出血性telangiectasias 1和2（分别为HHT1，HHT2）。 另外，ALK1和BMPRII中的人类突变与原发性肺动脉高压（PPH）有关。 在小鼠中，已证明ALK1和内源是血管生成所必需的。 综上所述，这些研究表明，内og（HHT1），ALK1（HHT2）和BMPRII（PPH）中的缺陷破坏了共同的信号通路。 C. Vary的已发表和初步数据支持这一假设和两个具体的目的：1）识别BMPRII介导的ALK1信号反应，以及2）检查内og和Alk1表达对血管模式的后果。这是一个高度创新的项目，很可能可以解决脉管系统中TGF-beta信号通路周围的一些悖论。这些研究是C.对内尾函数的细胞和分子生物学的长期兴趣的扩展。该项目与该鞋底的目标和目标高度相关，并且与项目1（Lindner）和2（LIAW）互动。可以预料，这些项目之间相当强烈的协作互动将继续发展。