INFLAMMATORY CELL SIGNALING BY CD36
CD36 的炎症细胞信号传导
基本信息
- 批准号:7337249
- 负责人:
- 金额:$ 39.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdipocytesApolipoprotein EApoptoticArterial Fatty StreakAtherosclerosisBlood VesselsCD36 geneCellsChronicComplementary DNAComplexDataDevelopmentDiabetes MellitusDiseaseElementsFoam CellsGoalsGrantHumanImmune systemIn VitroInflammationInflammatoryInflammatory ResponseInsulin ReceptorInsulin ResistanceKnockout MiceLesionLigandsLinkLipidsLipoprotein (a)Lipoprotein (a-)LipoproteinsLow-Density LipoproteinsMAPK8 geneMediatingMediator of activation proteinMetabolic PathwayMetabolic syndromeMitogen-Activated Protein KinasesMolecularMouse StrainsMusObesityPathogenesisPathway interactionsPhospholipidsPlayProcessPublishingRNA InterferenceReagentReceptor SignalingRoleSignal PathwaySignal TransductionTechnologyatherogenesiscell motilityinterestmacrophagemacrophage scavenger receptorsmigrationmonocyteoxidized lipidparticleprogramsreceptorreceptor functionresponsescavenger receptoruptake
项目摘要
THE
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Interaction of atherogenic lipids with vascular cells plays a critical role in the formation and progression of
atherosclerotic lesions. The goal of this project is to define the mechanisms by which CD36, a scavenger
receptor for specific forms of oxidized phospholipid, mediates pro-atherogenic and pro-inflammatory
responses. Recent studies suggest that scavenger receptor function in the vessel wall may be much more
complex than simply serving as a conduit for uptake of atherogenic LDL particles and that intracellular
signals triggered by the interaction of oxidized lipids with macrophage CD36 may induce responses that
contribute to lesion development and plaque instability. New data obtained during the previous grant period
shows that CD36-mediated signals led to activation of MAP kinases JNK-1 and -2. Given the central role of
JNK in mediating pro-inflammatory responses and new studies linking pathogenesis of diabetes and insulin
resistance to JNK activation, we propose that a CD36-dependent signaling pathway induced by the
interaction of specific oxidized phospholipids with macrophages and adipocytes contributes to
atherosclerosis and provides a mechanistic connection among atherosclerosis, inflammation, and insulin
resistance. To explore this hypothesis, we will take advantage of unique reagents and expertise available
through this new Program Project, including well characterized oxidized phospholipids that function as
specific CD36 ligands, multiple cd36 null mouse strains, and technologies to transduce primary monocytes
with cDNA and RNAi constructs. The 1st aim will define the role of specific oxidized lipid ligands in activating
macrophage CD36, identify the molecular elements of the CD36 signaling pathway in macrophages,
characterize the intracellular signaling pathways induced by CD36, and define the mechanisms by which
CD36 cross talks with other vascular cell receptor signaling pathways, focusing on receptors of the innate
immune system and insulin receptor. The 2nd aim will define mechanisms by which CD36 signals regulate
specific macrophage functions; e.g. lipoprotein and apoptotic cell uptake, modulation of the inflammatory
response, and cell migration.
的
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致动脉粥样硬化脂质与血管细胞的相互作用在动脉粥样硬化的形成和发展中起着关键作用。
动脉粥样硬化病变本项目的目标是定义清除剂CD 36
特定形式氧化磷脂的受体,介导促动脉粥样硬化和促炎症
应答最近的研究表明,血管壁中的清道夫受体功能可能更多
复杂,而不是简单地作为摄取致动脉粥样硬化的LDL颗粒的管道,
由氧化脂质与巨噬细胞CD 36相互作用触发的信号可诱导应答,
导致病变发展和斑块不稳定。上一个赠款期获得的新数据
显示CD 36介导的信号导致MAP激酶JNK-1和JNK-2的活化。由于核心作用,
JNK介导的促炎反应及糖尿病发病机制与胰岛素的关系
抗JNK激活,我们提出CD 36依赖性信号通路诱导的JNK激活,
特定氧化磷脂与巨噬细胞和脂肪细胞的相互作用有助于
并提供了动脉粥样硬化、炎症和胰岛素之间的机制联系
阻力为了探索这一假设,我们将利用现有的独特试剂和专业知识
通过这个新的计划项目,包括充分表征的氧化磷脂,
特异性CD 36配体、多种CD 36缺失小鼠品系和培养原代单核细胞的技术
用cDNA和RNAi构建体。第一个目标是确定特定的氧化脂质配体在激活
巨噬细胞CD 36,鉴定巨噬细胞中CD 36信号通路的分子元件,
表征由CD 36诱导的细胞内信号传导途径,并定义其机制,
CD 36与其他血管细胞受体信号传导途径交叉对话,重点关注先天性
免疫系统和胰岛素受体。第二个目标将定义CD 36信号调节的机制。
特异性巨噬细胞功能;例如脂蛋白和凋亡细胞摄取,炎症调节,
反应和细胞迁移。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Roy L Silverstein其他文献
Roy L Silverstein的其他文献
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{{ truncateString('Roy L Silverstein', 18)}}的其他基金
Regulation of the anti-angiogenic switch by CD36, Thrombospondin, and HRGP
CD36、血小板反应蛋白和 HRGP 调节抗血管生成开关
- 批准号:
7524585 - 财政年份:2008
- 资助金额:
$ 39.92万 - 项目类别:
Regulation of the anti-antiangiogenic switch by CD36, Thrombospondin, and HRGP
CD36、血小板反应蛋白和 HRGP 调节抗抗血管生成开关
- 批准号:
7642363 - 财政年份:2008
- 资助金额:
$ 39.92万 - 项目类别:
Regulation of the anti-antiangiogenic switch by CD36, Thrombospondin, and HRGP
CD36、血小板反应蛋白和 HRGP 调节抗抗血管生成开关
- 批准号:
8269065 - 财政年份:2008
- 资助金额:
$ 39.92万 - 项目类别:
Regulation of the anti-antiangiogenic switch by CD36, Thrombospondin, and HRGP
CD36、血小板反应蛋白和 HRGP 调节抗抗血管生成开关
- 批准号:
7858475 - 财政年份:2008
- 资助金额:
$ 39.92万 - 项目类别:
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