Anti-angiogenic signaling molecules in retinal cells

视网膜细胞中的抗血管生成信号分子

• 批准号: 6415729
• 负责人: Nader Rahimi
• 金额: $ 16.21万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415729
• 关键词: Sf9 cell line; angiogenesis; angiogenesis inhibitors; biological signal transduction; complementary DNA; expression cloning; gene expression; gene induction /repression; genetic library; immunoprecipitation; microarray technology; northern blottings; polymerase chain reaction; regulatory gene; site directed mutagenesis; vascular endothelial growth factors; vascular endothelium

Angiogenesis, formation of new blood vessels from pre-existing vessels is a hallmark of many eye diseases such as age-related macular degeneration, proliferative diabetic retinopathy, retinopathy of prematurity and vascular glaucoma, which are among leading cause of visual loss in the USA and throughout the world. Vascular endothelial growth factor (VEGF), the major stimulator of angiogenesis, elicits its effect by binding to and activating two endothelial receptors namely VEGFR-1/FLK-1 and VEGFR-2/FLT-1. Although activation of VEGFR-2 has been demonstrated to be an essential requirement for induction of angiogenesis, the role of VEGFR-1 in angiogenesis is largely unknown. We will investigate the molecular mechanisms responsible for action of VEGFR-1, such as activation of signaling molecules or induction of immediate early genes (IEG) that might drive its anti-angiogenesis effects in endothelial cells. The significance of the results obtained from the proposed study lies in their potential to provide fundamental information on how VEGFR-1 communicates to control/restrain angiogenesis in endothelial cells. The importance of angiogenesis in ocular diseases is well recognized. our long-term goal is to begin to apply the information obtained from this project to the design of strategies to regulate angiogenesis in clinical settings.

血管生成，即从已有血管形成新血管，是许多眼部疾病的标志，例如年龄相关性黄斑变性、增殖性糖尿病视网膜病变、早产儿视网膜病变和血管性青光眼，这些疾病是美国和全世界视力丧失的主要原因之一。血管内皮生长因子 (VEGF) 是血管生成的主要刺激剂，通过结合并激活两种内皮受体（即 VEGFR-1/FLK-1 和 VEGFR-2/FLT-1）来发挥作用。尽管 VEGFR-2 的激活已被证明是诱导血管生成的必要条件，但 VEGFR-1 在血管生成中的作用很大程度上未知。我们将研究负责 VEGFR-1 作用的分子机制，例如信号分子的激活或立即早期基因 (IEG) 的诱导，这些可能驱动其在内皮细胞中的抗血管生成作用。从拟议的研究中获得的结果的重要性在于它们有可能提供关于 VEGFR-1 如何通信以控制/抑制内皮细胞中血管生成的基本信息。血管生成在眼部疾病中的重要性已得到广泛认可。我们的长期目标是开始将从该项目获得的信息应用于临床环境中调节血管生成的策略设计。