Notch and TGF-beta in the Control of Retinal Vascular Integrity

Notch 和 TGF-β 控制视网膜血管完整性

基本信息

批准号：
8843865
负责人：
Joseph Arboleda-Velasquez
金额：
$ 24.03万
依托单位：
SCHEPENS EYE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8843865
关键词：
Address Affect Autopsy Award Background Diabetic Retinopathy Basement membrane Biotin Biotinylation Blindness Blood Vessels Blood capillaries Cell Communication Cell Culture System Cell Culture Techniques Cell Survival Cells Cellular Membrane Clinical Coculture Techniques Complications of Diabetes Mellitus Data Development Diabetes Mellitus Diabetic Microangiopathies Diabetic Retinopathy Diabetic mouse Dropout Endothelial Cells Environment Event Eye Genetic Epistasis Glucose Human Hyperglycemia Investments Label Ligands Location Measures Mediating Mentors Microvascular Dysfunction Molecular Output Pathology Pericytes Phase Play Publishing Research Research Proposals Retina Retinal Role Signal Pathway Signal Transduction Site Staging Streptozocin System Testing Tissues Training Training Support Transforming Growth Factor beta Work assay development base blood glucose regulation capillary career cell type diabetic genetic approach human tissue imaging modality in vivo Model mouse model notch protein receptor research study vascular bed

项目摘要

ABSTRACT Diabetic retinopathy is among the most common complications of diabetes. Basement membrane thickening and pericyte loss are early changes associated with the development of diabetic retinopathy. I speculate that these events disrupt Notch signaling, which depends upon juxtaposition of cellular membranes, and also impair cell signaling cross-talk between Notch and TGF-ß signaling. To test this hypothesis, I propose to: (i) establish a cell culture system to measure cell-cell interactions mediated by Notch using imaging methods; (ii) examine how Notch/TGF-ß signaling is affected in vascular cells cultured under conditions resembling a diabetic environment; and, (iii) use mouse models and postmortem human eye tissue for examining the role of Notch/TGF-ß interactions in diabetic retinopathy. I propose a training plan that will enable me to accomplish the proposed experiments and a strategy for transition towards career independence.

抽象的糖尿病视网膜病变是糖尿病最常见的并发症之一。我推测，周细胞丢失是与糖尿病视网膜病变发展相关的早期变化。这些事件会破坏依赖于细胞膜并置的 Notch 信号传导，并且还会损害 Notch 和 TGF-β 信号之间的细胞信号串扰为了检验这一假设，我建议：(i) 建立。使用成像方法测量 Notch 介导的细胞间相互作用的细胞培养系统；在类似糖尿病的条件下培养的血管细胞中 Notch/TGF-ß 信号如何受到影响环境；以及，(iii) 使用小鼠模型和死后人眼组织来检查其作用 Notch/TGF-β 在糖尿病视网膜病变中的相互作用我提出了一个训练计划，该计划将使我能够完成任务。拟议的实验和向职业独立过渡的战略。