Forkhead Signaling in the Endothelium

内皮细胞中的叉头信号传导

基本信息

批准号：
7426364
负责人：
William C Aird
金额：
$ 40.3万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7426364
关键词：
Agonist Apoptosis Apoptotic Attenuated Biological Biology Blood Vessels Cell Cycle Arrest Cell Cycle Progression Cell Cycle Regulation Cell Nucleus Cell physiology Cells Cessation of life Class Complex Coupled Coupling Data Disease Disruption Embryo Endothelial Cells Endothelium Environment Equilibrium Exclusion FOXO1A gene Family Foundations Functional disorder GADD45A gene Gadd45a protein Gene Expression Gene Expression Alteration Gene Targeting Genes Genetic Goals Growth Growth Factor Health Heterogeneity Homeostasis Human In Vitro Investigation Knock-out Link Literature Manganese Superoxide Dismutase Mediating Mediator of activation protein Modality Molecular Mus Nuclear Output Pathway interactions Pattern Phenotype Phosphorylation Play Polymerase Chain Reaction Protein Isoforms Protein Overexpression RNase protection assay Reporting Repression Research Personnel Role Signal Pathway Signal Transduction Small Interfering RNA TNF gene Therapeutic Thrombin Time Transducers Vascular Diseases Vascular Endothelial Growth Factors cytokine design extracellular forkhead protein in vivo inhibitor/antagonist insight migration preconditioning programs research study response transcription factor

项目摘要

DESCRIPTION (provided by applicant): Endothelial cell phenotypes display remarkable heterogeneity in health and disease. An important goal in vascular biology is to understand the molecular mechanisms underlying the spatial and temporal modulation of endothelial cell phenotypes. We have recently demonstrated that: 1) forkhead transcription factors are constitutively expressed in endothelial cells, 2) VEGF, TNF-a and thrombin induce the phosphorylation of 1 or more of the forkhead proteins in primary human endothelial cells, and 3) the inducible phosphorylation of forkhead transcription factors is coupled to a reduction in target gene expression and alteration in endothelial cell function. Taken together, this data supports the hypothesis that forkhead transcription factors function as signal transducers in the endothelium, coupling short-term changes in the extracellular environment to downstream changes in gene expression. The overall goal of this project is to characterize the role for forkhead transcription factors in transducing extracellular signals within the endothelium. A more complete understanding of these mechanisms should provide a framework for tailoring and fine tuning therapeutic modalities in vascular disease states.

描述（由申请人提供）：内皮细胞表型在健康和疾病中表现出显着的异质性。血管生物学的一个重要目标是了解内皮细胞表型的空间和时间调节的基础分子机制。我们最近证明：1）在内皮细胞中组成型转录因子，2）2）VEGF，TNF-A和凝血酶在原代人内皮细胞中诱导1或更多叉头蛋白的磷酸化，以及3）可诱导的磷酸化磷酸化。叉状转录因子的耦合与内皮细胞功能的靶基因表达和改变的降低。综上所述，该数据支持以下假设：叉状转录因子在内皮中充当信号换能器，将细胞外环境中的短期变化与基因表达的下游变化耦合。该项目的总体目的是表征叉状转录因子在内皮内部转导细胞外信号中的作用。对这些机制的更全面了解应为血管疾病状态下的调整和微调治疗方式提供一个框架。