SC COBRE: SPHINGOSINE1PHOSPHATE IN EARLY BLOOD VESSEL FORMATION

SC COBRE：早期血管形成中的磷酸鞘氨醇

• 批准号: 7381846
• 负责人: KELLEY M ARGRAVES
• 金额: $ 7.13万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381846
• 关键词: SC; COBRE; SPHINGOSINE1PHOSPHATE; EARLY; BLOOD

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. Sphingosine-1-phosphate (S1P) is a phosphorylated sphingolipid whose signaling is mediated by G protein-coupled receptors. Research in this project focuses on investigating the role of S1P signaling in the process of de novo formation of embryonic blood vessel, vasculogenesis. At stages preceding the formation of blood vessels (i.e., 7.5-8 dpc) in the embryo proper, yolk sac and allantois we have found that the S1P receptor S1P2 is expressed in conjunction with S1P1 and/or S1P3. Using the cultured mouse allantois explant model of blood vessel formation, we find that vasculogenesis is dependent on S1P signaling. We also have found that S1P can replace the requirement of serum for promoting vasculogenesis in cultured allantois explants. Instead, of small, poorly reticulated clusters of endothelial cells that formed under serum-free conditions, S1P promoted the formation of expansive, branched networks of capillary-like vessels. These effects could not be mimicked administration of growth factors such as VEGF or bFGF. Additionally, we have found that the ability of S1P to promote blood vessel formation is not due to it having effects on cell survival or eliciting changes in numbers of endothelial cells, angioblasts (endothelial precursor cells) or mesodermal cells (angioblast progenitor cells). Taken together, our findings indicate that S1P signaling is critically important for promoting migratory activities of angioblasts and early endothelial cells that are required for the expansion of nascent vascular networks. Research is currently focused on delineating the mechanisms by which S1P influences migratory activities of these cells during vasculogenesis. Emphasis is being placed on characterizing effects of S1P on the expression of proteins associated with cell motility (i.e., integrin adhesion receptors, their ligands and intracellular effectors of cell migration).

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。鞘氨醇-1-磷酸（S1 P）是一种磷酸化鞘脂，其信号传导由G蛋白偶联受体介导。本项目的研究重点是探讨S1 P信号在胚胎血管新生过程中的作用。在血管形成之前的阶段（即，7.5- 8dpc）的胚胎、卵黄囊和尿囊中，我们发现S1 P受体S1 P2与S1 P1和/或S1 P3一起表达。利用培养的小鼠尿囊外植体血管形成模型，我们发现血管发生依赖于S1 P信号。我们还发现S1 P可以代替血清促进培养的尿囊外植体中的血管发生。相反，在无血清条件下形成的小的、网状结构差的内皮细胞簇，S1 P促进了毛细血管样血管的扩张的、分支的网络的形成。这些作用无法通过给予生长因子（例如VEGF或bFGF）来模拟。此外，我们发现S1 P促进血管形成的能力不是由于其对细胞存活的影响或引起内皮细胞、成血管细胞（内皮前体细胞）或中胚层细胞（成血管细胞祖细胞）数量的变化。总之，我们的研究结果表明，S1 P信号是至关重要的促进迁移活动的成血管细胞和早期内皮细胞所需的新生血管网络的扩展。目前的研究集中在描绘S1 P影响这些细胞在血管发生过程中的迁移活动的机制。重点放在表征S1 P对与细胞运动性相关的蛋白质表达的影响（即，整联蛋白粘附受体、它们的配体和细胞迁移的细胞内效应物）。