Regulation of Vascular Inflammation by ESE-1
Regulation of Vascular Inflammation by ESE-1
批准号:
6650340
负责人:
J Peter PETER OETTGEN
金额:
$34.0万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-09-01 至 2005-08-31
中文摘要
描述(申请人摘要):炎症,动脉粥样硬化的标志
和其他血管疾病,其特征在于激活几个
基因包括细胞因子、粘附分子、环加氧酶和一氧化氮合酶,
氧化物合酶这些研究的长期目标是确定关键的
血管生成和增殖所需的决定因素
炎症我们的方法来解开潜在的分子机制
血管炎症是为了确定转录因子,
这些回应。已知转录因子的NF-κ B家族是
这些事件的关键媒介。我们发现了一种新的外星人
一种转录因子ESE- 1,响应于白细胞介素-1而被诱导
血管平滑肌中的β、肿瘤坏死因子α和内毒素
细胞、内皮细胞和单核细胞。这种归纳至少在一定程度上
由NF-κ B介导。ESE-1在Ets因子中是独特的,因为它具有两个
在HMG中发现的DNA结合结构域、经典Ets结构域和A/T钩结构域
proteins.我们的研究结果表明,ESE-1的两个DNA结合结构域可以
与NF-κ B的p50亚基结合。我们已经确定了诱导型
一氧化氮合酶(NOS 2)作为ESE-I的靶标。ESE-1是一种强大的
NOS 2基因启动子的反式激活因子和ESE-1导入细胞
可以激活NOS 2基因的表达。在大鼠内毒素血症模型中,
在急性血管炎症中,ESE- 1在血管平滑肌中被强烈诱导,
肌肉细胞和内皮细胞。这些研究的假设是,
Ets因子ESE-1是血管炎症的转录介质。
这项研究的具体目标是:
I.定义ESE-1作为转录激活因子的生物学作用,
NOS 2基因和其他与血管炎症相关的基因。
二.确定DNA结合特异性和功能的重要性,
两个ESE-1 DNA结合结构域。
三.确定ESE-1表达对血管细胞的生物学效应
功能
用于实现这些目标的方法和模型包括电泳
迁移率变动分析,免疫组织化学,转录谱,动物
血管炎症模型和转基因模型。的结果予以
研究应该提供新的见解的分子机制参与
调节血管炎症并提供潜在的新治疗途径
用于治疗血管疾病,例如动脉粥样硬化、再狭窄和
与移植相关的血管病变。
英文摘要
DESCRIPTION (Applicant's abstract): Inflammation, a hallmark of atherosclerosis
and other vascular diseases, is characterized by the activation of several
genes including cytokines, adhesion molecules, cyclooxygenases, and nitric
oxide synthase. The long term goal of these studies is to identify the critical
determinants required for the initiation and propagation of vascular
inflammation. Our approach to unraveling the molecular mechanisms underlying
vascular inflammation is to identify the transcription factors that regulate
these responses. The NF-kappa B family of transcription factors are known to be
critical mediators of these events. We have identified a novel Ets
transcription factor ESE- 1, that is induced in response to interleukin- 1
beta, tumor necrosis factor alpha, and endotoxin in vascular smooth muscle
cells, endothelial cells and monocytes. This induction is at least in part
mediated by NF-kappa B. ESE-1 is unique among Ets factors in that it has two
DNA binding domains, a classical Ets domain and an A/T hook domain found in HMG
proteins. Our results demonstrate that both DNA binding domains of ESE-1 can
bind to the p50 subunit of NF-kappa B. We have identified the inducible form of
nitric oxide synthase (NOS2) as a target for ESE-l. ESE-1 is a strong
transactivator of the NOS2 gene promoter and introduction of ESE-1 into cells
can activate NOS2 gene expression. In a rat model of endotoxemia associated
with acute vascular inflammation, ESE- 1 is strongly induced in vascular smooth
muscle cells and endothelial cells. The hypothesis for these studies is that
the Ets factor ESE-1 is a transcriptional mediator of vascular inflammation.
The specific aims of the study are to:
I. Define the biological role of ESE-1 as a transcriptional activator of the
NOS2 gene and other genes associated with vascular inflammation.
II. Determine the DNA binding specificity and the functional importance of the
two ESE-1 DNA binding domains.
III. Determine the biological effect of ESE-1 expression on vascular cell
function.
The methods and models used to achieve these goals include electrophoretic
mobility shift assays, immunohistochemistry, transcriptional profiling, animal
models of vascular inflammation, and transgenic models. The results of these
studies should provide new insights into the molecular mechanisms involved in
regulating vascular inflammation and provide potential new therapeutic avenues
for treatment of vascular diseases such as atherosclerosis, restenosis, and the
vasculopathy associated with transplantation.
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The Role of Ets-1 in Vascular Inflammation
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资助金额:$42.88万
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The Role of Angiopoietin-1 in Rheumatoid Arthritis
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批准号:6917103
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The Role of Angiopoietin-1 in Rheumatoid Arthritis
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批准号:7097406
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资助金额:$25.13万
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财政年份:2002
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Regulation of Vascular Inflammation by ESE-1
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批准号:6528015
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项目类别:
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资助金额:$34.0万
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财政年份:2001
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负责人:J Peter PETER OETTGEN
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依托单位:
Regulation of Vascular Inflammation by ESE-1
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批准号:6320586
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项目类别:
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资助金额:$34.0万
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财政年份:2001
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负责人:J Peter PETER OETTGEN
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依托单位:
Regulation of Vascular Inflammation by ESE-1
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批准号:6784159
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资助金额:$34.0万
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财政年份:2001
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负责人:J Peter PETER OETTGEN
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ETS FACTOR NERF AND VASCULOGENESIS
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财政年份:1999
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ETS FACTOR NERF AND VASCULOGENESIS
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财政年份:1999
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负责人:J Peter PETER OETTGEN
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ETS FACTOR NERF AND VASCULOGENESIS
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资助金额:$37.19万
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财政年份:1999
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ETS FACTOR NERF AND VASCULOGENESIS
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资助金额:$24.03万
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ETS FACTOR NERF AND B CELL FUNCTION
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财政年份:1996
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依托单位:
ETS FACTOR NERF AND B CELL FUNCTION
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资助金额:$8.79万
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财政年份:1996
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负责人:J Peter PETER OETTGEN
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依托单位:
ETS FACTOR NERF AND B CELL FUNCTION
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批准号:2517732
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项目类别:
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资助金额:$7.72万
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财政年份:1996
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依托单位:
ETS FACTOR NERF AND B CELL FUNCTION
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资助金额:$8.79万
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财政年份:1996
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依托单位:
海外基金