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,其特点是激活几个
细胞因子、黏附分子、环氧合酶和一氧化氮等基因
氧化物合成酶。这些研究的长期目标是确定关键的
维管束的启动和繁殖所需的决定因素
发炎。我们解开潜在分子机制的方法
血管炎症是确定调节血管炎症的转录因子
这些回应。已知的核因子-kappa B转录因子家族是
这些事件的关键调解人。我们发现了一种新的外星人
转录因子ESE-1,受白介素1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。这种归纳至少部分是
由核因子-kappa B介导,ESE-1在ETS因子中是独一无二的,因为它有两个
HMG中发现的DNA结合域、经典Ets结构域和A/T挂钩结构域
蛋白质。我们的结果表明,ESE-1的两个DNA结合域都可以
结合到核因子-kappaB的p50亚基上。我们已经鉴定了
一氧化氮合酶(NOS2)作为ESE-L的靶标。ESE-1是一种强大的
NOS2基因启动子反式激活因子及ESE-1基因导入细胞
能激活NOS2基因的表达。在与内毒素血症相关的大鼠模型中
在急性血管炎症中,ESE-1在血管平滑中被强烈诱导
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。
这项研究的具体目的是:
I.确定ESE-1作为转录激活因子的生物学作用
NOS2等与血管炎症相关的基因。
II.确定DNA结合的特异性和功能重要性
两个ESE-1 DNA结合区。
三、确定ESE-1表达对血管细胞的生物学效应
功能。
实现这些目标所使用的方法和模型包括
迁移率变化分析、免疫组织化学、转录图谱、动物
血管炎症模型和转基因模型。这些研究的结果
研究应该为参与的分子机制提供新的见解
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,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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批准号:7683745
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项目类别:
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资助金额:$42.88万
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财政年份:2008
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负责人:J Peter PETER OETTGEN
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依托单位:
The Role of Ets-1 in Vascular Inflammation
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批准号:7914137
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资助金额:$42.31万
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财政年份:2008
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The Role of Ets-1 in Vascular Inflammation
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批准号:7457483
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资助金额:$45.23万
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财政年份:2008
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THE MOLECULAR MECHANISMS OF ENDOTHELIAL DIFFERENTATION
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批准号:6946581
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财政年份:2004
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负责人:J Peter PETER OETTGEN
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依托单位:
The Role of Angiopoietin-1 in Rheumatoid Arthritis
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批准号:6778152
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资助金额:$27.97万
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财政年份:2002
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负责人:J Peter PETER OETTGEN
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依托单位:
The Role of Angiopoietin-1 in Rheumatoid Arthritis
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批准号:6544885
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项目类别:
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资助金额:$27.97万
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财政年份:2002
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负责人:J Peter PETER OETTGEN
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依托单位:
The Role of Angiopoietin-1 in Rheumatoid Arthritis
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批准号:6660300
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项目类别:
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资助金额:$27.97万
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财政年份:2002
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负责人:J Peter PETER OETTGEN
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依托单位:
The Role of Angiopoietin-1 in Rheumatoid Arthritis
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批准号:6917103
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项目类别:
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资助金额:$25.73万
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财政年份:2002
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负责人:J Peter PETER OETTGEN
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依托单位:
The Role of Angiopoietin-1 in Rheumatoid Arthritis
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批准号:7097406
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项目类别:
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资助金额:$25.13万
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财政年份:2002
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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
-
批准号:6528015
-
项目类别:
-
资助金额:$34.0万
-
财政年份:2001
-
负责人:J Peter PETER OETTGEN
-
依托单位:
Regulation of Vascular Inflammation by ESE-1
-
批准号:6320586
-
项目类别:
-
资助金额:$34.0万
-
财政年份:2001
-
负责人:J Peter PETER OETTGEN
-
依托单位:
Regulation of Vascular Inflammation by ESE-1
-
批准号:6784159
-
项目类别:
-
资助金额:$34.0万
-
财政年份:2001
-
负责人:J Peter PETER OETTGEN
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依托单位:
ETS FACTOR NERF AND VASCULOGENESIS
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批准号:2883994
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项目类别:
-
资助金额:$24.46万
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财政年份:1999
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负责人:J Peter PETER OETTGEN
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依托单位:
ETS FACTOR NERF AND VASCULOGENESIS
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批准号:6390416
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项目类别:
-
资助金额:$36.11万
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财政年份:1999
-
负责人:J Peter PETER OETTGEN
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依托单位:
ETS FACTOR NERF AND VASCULOGENESIS
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批准号:6527345
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项目类别:
-
资助金额:$37.19万
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财政年份:1999
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负责人:J Peter PETER OETTGEN
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依托单位:
ETS FACTOR NERF AND VASCULOGENESIS
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批准号:6185064
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项目类别:
-
资助金额:$24.03万
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财政年份:1999
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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:2115057
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项目类别:
-
资助金额:$7.72万
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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:6172976
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项目类别:
-
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:2895587
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项目类别:
-
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:
-
资助金额:$7.72万
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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:
海外基金