Sphingosine-1-phosophate signaling in vasculogenesis

1-磷酸鞘氨醇信号传导在血管发生中的作用

• 批准号: 6908722
• 负责人: KELLEY M ARGRAVES
• 金额: $ 31.7万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908722
• 关键词: angiogenesis; biological signal transduction; blood circulation; cell motility; cell surface receptors; genetically modified animals; integrins; laboratory mouse; myocardial infarction; neoplasm /cancer blood supply; neoplastic growth; phosphates; polymerase chain reaction; sphingosine; tissue /cell culture; vascular smooth muscle; wound healing

DESCRIPTION (provided by applicant): Sphingosine-1-phosphate (S1P) is a phosphorylated sphingolipid that mediates signaling via G-protein-coupled receptors. S1P signaling promotes an array of vascular cell behaviors important in angiogenesis and smooth muscle cell investment of nascent blood vessels. S1P signaling has not been considered to play an important role in the process of de novo formation of blood vessels, vasculogenesis. However, our recent findings indicate that vasculogenesis is dependent on S1P signaling. Specifically, S1P signaling is critical to promote migratory activities of angioblasts required for the expansion of vascular networks. A major tenet of this research project is that S1P-dependent angioblast motility has broad relevance to neovascular events in the embryo and adult. Not only can S1P-dependent angioblast motility be an important mechanism by which nascent embryonic vascular networks expand, but it may also be a critical aspect of the assembly of adult blood vessels from blood-derived endothelial cell progenitors/angioblasts. It is therefore necessary to understand the mechanisms by which S1P signaling influences angioblast motility and to establish its in vivo relevance in the context of physiological and pathological neovascular processes that involve adult vasculogenesis including tumor formation, wound healing and myocardial infarction. To address these objectives there are 3 specific aims: 1. Identify the specific S1P receptor(s) that are critical for mediating S1P signaling during vasculogenesis, 2. Characterize the involvement of integrins in S1P-induced angioblast motility, and 3. Determine the significance S1P signaling to adult vasculogenesis mediated by circulating angioblasts.

描述（由申请人提供）：1-磷酸鞘氨醇（S1 P）是一种磷酸化鞘脂，通过G蛋白偶联受体介导信号传导。S1 P信号转导促进一系列在新生血管的血管生成和平滑肌细胞投资中重要的血管细胞行为。S1 P信号转导在血管新生过程中并没有发挥重要作用。然而，我们最近的研究结果表明，血管发生是依赖于S1 P信号。具体而言，S1 P信号传导对于促进血管网络扩张所需的成血管细胞的迁移活动至关重要。该研究项目的一个主要原则是S1 P依赖性成血管细胞运动与胚胎和成人的新生血管事件具有广泛的相关性。S1 P依赖的成血管细胞运动不仅可以是新生胚胎血管网络扩展的重要机制，而且它也可能是来自血液来源的内皮祖细胞/成血管细胞的成人血管组装的关键方面。因此，有必要了解S1 P信号传导影响成血管细胞运动的机制，并建立其在生理和病理新生血管过程的背景下，涉及成人血管发生，包括肿瘤形成，伤口愈合和心肌梗死的体内相关性。为了实现这些目标，有三个具体目标：1。确定在血管发生过程中对介导S1 P信号传导至关重要的特异性S1 P受体，2。描述...的参与 整合素在S1 P诱导的成血管细胞运动中的作用，以及3.确定S1 P信号对循环成血管细胞介导的成人血管发生的意义。