CONTROL OF VEGF STIMULATED ENDOTHELIAL PROLIFERATION

与糖尿病相关的新血管形成是糖尿病患者新血管形成的主要原因。 2 - 74岁的人失明。 预防和治疗新生血管 糖尿病视网膜病变等疾病更有效，有一个 明确需要在细胞内更好地了解血管生成 和分子水平。 申请人指出， 他的研究计划是了解事件的顺序， 当正常静止的血管内皮细胞（EC） 分化成增殖的血管生成表型。 研究 在申请中提出的将集中在核RNA结合蛋白 一个名为猪圈的地方， 事件 EC猪圈首先在申请人的实验室中分离， 它对多糖的亲和力。 申请人报告说， 这种核凝集素的表达在EC表型过程中受到严格的调节， 过渡 最近的实验表明，血管内皮细胞 血管内皮生长因子（VEGF）治疗EC会引发 猪圈，猪圈拮抗剂阻断VEGF刺激增殖， 说明猪舍在食管癌RNA代谢中起重要作用 增殖 该项目的第一个目标是建立一个功能 VEGF与猪舍的关系 第二个目标是确定 猪圈结合转录本，并确定它们是否代表EC特异性 或普遍存在的基因。 申请人指出，在初步工作中， 他的研究小组已经分离并克隆了一群猪圈结合RNA 防止EC扩散。 将使用标准的 测序技术和核酸数据库。 申请人 提出了第三个目标，以测试假设，猪圈发挥了作用， EC增殖过程中的RNA生物合成。 一系列猪舍拮抗剂 将被显微注射或转染到细胞中。 北方分析和 然后将使用原位杂交来跟踪合成， 处理和对照中特定转录物的加工和运输 细胞

Neovascularization associated with diabetes is the leading cause of new blindness in people age 2-74. To prevent and treat neovascular disorders such as diabetic retinopathy more effectively, there is a clear need to develop a better knowledge of angiogenesis at the cellular and molecular levels. The applicant states that the long-term goal of his research program is to understanding the sequence of events that occur when normally quiescent vascular endothelial cells (EC) differentiate into a proliferative, angiogenic phenotype. The study proposed in the application will focus on a nuclear RNA binding protein named pigpen that appears to lie directly in the pathway of these events. EC pigpen was first isolated in the applicant's laboratory by its affinity for polysaccharides. The applicant reports that expression of this nuclear lectin is sharply regulated during EC phenotype transition. Recent experiments have shown that vascular endothelial growth factor (VEGF) treatment of EC triggers a redistribution of pigpen, that pigpen antagonists block VEGF-stimulated proliferation, and that pigpen may play an essential role in RNA metabolism during EC proliferation. The first aim of this project is to establish a function link between VEGF and pigpen. The second aim will be to identify pigpen-binding transcripts and determine if they represent EC-specific or ubiquitous genes. The applicant states that, in preliminary work, his group has isolated and cloned a population of pigpen-binding RNAs from proliferating EC. This library will be analyzed using standard sequencing techniques and nucleic acid databases. The applicant proposes a third aim to test the hypothesis that pigpen plays a role in RNA biogenesis during EC proliferation. A series of pigpen antagonists will be microinjected or transfected into cells. Northern analysis and in situ hybridization will then be used to track the synthesis, processing, and transport of specific transcripts in treated and control cells.