Elucidating the role of neuropilin-mediated intercellular adhesion in tissue vascularisation

阐明神经毡蛋白介导的细胞间粘附在组织血管化中的作用

• 批准号: G0601093/1
• 负责人: Christiana Ruhrberg
• 金额: $ 45.52万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601093%2F1
• 关键词: Elucidating; role; neuropilin; mediated; intercellular

A large number of conditions such as heart ischemia, diabetic limb neuropathy and several neurodegenerative diseases are characterized by oxygen-deficiency in vital organs. Reagents are continually being developed that modulate the activity of the critical blood vessel growth factor VEGF and its receptors for use in medical therapies aimed at restoring blood supply to such oxygen-deficient organs. However, in several recent mouse models, VEGF delivery resulted in the formation of dangerously tortuous and leaky vessels that were poorly integrated into the surrounding tissue. We therfore need to undestand better how VEGF signals are interpreted by their blood vessel receptors in healthy organs, and how VEGF signals are integrated with other signaling pathway to ensure the coordinated and productive vessel invasion into the oxygen-deficient tissues. The project described in this proposal will determine how the cell surface protein NRP1 functions during blood vessel development. Understanding NRP1 activity is particularly important, because this protein is likely to perform a dual function during blood vessel growth, firstly, as a VEGF receptor, and, secondly, as a mediator of cell-to-cell adhesion between growing vessels and the tissues they invade in response to VEGF signals.

心脏缺血、糖尿病肢体神经病变和几种神经退行性疾病等大量疾病的特征是重要器官的缺氧。正在不断开发调节关键血管生长因子血管内皮生长因子及其受体活性的试剂，用于旨在恢复此类缺氧器官血液供应的医疗治疗。然而，在最近的几个小鼠模型中，血管内皮生长因子的传递导致了危险的曲折和泄漏的血管的形成，这些血管与周围组织的整合很差。因此，我们需要更好地了解在健康器官中血管受体如何解释血管内皮生长因子信号，以及血管内皮生长因子信号如何与其他信号通路整合，以确保血管协同高效地侵入缺氧组织。该提案中描述的项目将确定细胞表面蛋白Nrp1在血管发育过程中的功能。了解Nrp1的活性尤为重要，因为该蛋白可能在血管生长过程中发挥双重功能，首先是作为血管内皮生长因子受体，其次是作为细胞间黏附的媒介，在生长的血管和它们响应血管信号而侵入的组织之间进行细胞间黏附。