CD40 monocyte in chronic kidney disease
CD40单核细胞在慢性肾脏病中的作用
基本信息
- 批准号:9897533
- 负责人:
- 金额:$ 71.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-01 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAntibodiesAortaApolipoprotein EAtherosclerosisBloodBlood VesselsCD14 geneCD40 LigandCardiovascular DiseasesCardiovascular systemCell surfaceCellsCessation of lifeCholesterolChronicChronic Kidney FailureDNADNA MethylationDataDevelopmentDiseaseEnd stage renal failureFCGR3B geneFolic AcidGeneral PopulationGlucoseHomocysteineHumanHyperhomocysteinemiaImmuneInfiltrationInflammasomeInflammationInflammation MediatorsInflammatoryKnowledgeLeadLinkMediator of activation proteinMetabolicMethylationMolecularMusNephrectomyPathogenesisPatientsPeripheral Blood Mononuclear CellPhagocytesPhenotypePopulationProceduresProductionReagentRenal functionReportingResearchRisk FactorsRoleSeverity of illnessSpleenSplenocyteStimulusTNFRSF5 geneTestingTherapeuticTissuesToxinTransplantationVascular DiseasesVascular remodelingbasecytokinehuman modelimprovedinhibitor/antagonistmonocytemortalitymouse modelnew therapeutic targetnovelnovel therapeuticspreventpromoterresponsesuccesstherapeutic evaluationvascular inflammation
项目摘要
Summary:
Chronic kidney disease (CKD) is a common disease affecting >15% of the US adult population and
has cardiovascular mortality10- to 30-folds greater than that in general population. We recently
discovered a novel inflammatory monocyte subset the CD40 monocyte (MC) that has strong
inflammatory feature and is elevated in CKD patients. We determined CD40+ MC as a novel
inflammatory MC subset which is elevated in CKD subjects. Additional preliminary data lead us to
hypothesize that CKD and uremic toxins induce CD40+ inflammatory MC differentiation via CD40 ligand
induced CD40 expression, DNA hypomethylation on CD40 promoter, and 2) CD40 Inhibition,
inflammasome suppression and DNA methylation therapy can reverse CD40+ MC differentiation,
vascular inflammation and atherosclerosis. We will test this hypothesis using three connected Aims. Aim
1 will investigate the effect of CKD on CD40+ MC differentiation and tissue inflammation in human and
mouse models of CKD, and in uremic toxin-treated human/mouse PBMC. Aim 2 will examine
molecular mechanism underlying CKD-induced CD40+ MC differentiation. Aim 3 will test the
therapeutic benefit of CD40 blocking, Casp1 inhibition and DNA methylation on CD40+ MC
differentiation, atherosclerosis and kidney function in CKD. Accomplishment of the proposed research
will lead to the identification of fundamental mechanistic links between CKD and cardiovascular
disease, and novel therapeutic targets.
总结:
慢性肾病(CKD)是一种常见疾病,影响>15%的美国成年人口,
心血管死亡率是普通人群的10 - 30倍。我们最近
发现了一种新的炎性单核细胞亚群CD 40单核细胞(MC),
炎症特征,并在CKD患者中升高。我们确定CD 40 + MC为一种新的
在CKD受试者中升高的炎性MC亚群。额外的初步数据使我们
假设CKD和尿毒症毒素通过CD 40配体诱导CD 40+炎性MC分化
诱导的CD 40表达,CD 40启动子上的DNA低甲基化,和2)CD 40抑制,
炎性小体抑制和DNA甲基化治疗可以逆转CD 40 + MC分化,
血管炎症和动脉粥样硬化。我们将用三个相互关联的目标来检验这个假设。目的
1将研究CKD对人CD 40 + MC分化和组织炎症的影响,
慢性肾脏病小鼠模型以及尿毒症毒素处理的人/小鼠外周血单个核细胞中。目标2将检查
CKD诱导CD 40 + MC分化的分子机制目标3将测试
CD 40阻断、Casp 1抑制和DNA甲基化对CD 40 + MC的治疗益处
分化、动脉粥样硬化和肾功能。完成拟议的研究
将导致确定CKD和心血管疾病之间的基本机制联系
疾病和新的治疗靶点。
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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Hong Wang其他文献
Hong Wang的其他文献
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{{ truncateString('Hong Wang', 18)}}的其他基金
Mechanisms of inflammation-triggered taste loss and its recovery
炎症引发的味觉丧失及其恢复机制
- 批准号:
10359837 - 财政年份:2021
- 资助金额:
$ 71.4万 - 项目类别:
Core 2: Biostatistics and Bioinformatics Core
核心2:生物统计学和生物信息学核心
- 批准号:
10469634 - 财政年份:2021
- 资助金额:
$ 71.4万 - 项目类别:
Mechanisms of inflammation-triggered taste loss and its recovery
炎症引发的味觉丧失及其恢复机制
- 批准号:
10211925 - 财政年份:2021
- 资助金额:
$ 71.4万 - 项目类别:
Core 2: Biostatistics and Bioinformatics Core
核心2:生物统计学和生物信息学核心
- 批准号:
10683755 - 财政年份:2021
- 资助金额:
$ 71.4万 - 项目类别:
Mechanisms of long-term taste loss in post-acute sequelae of COVID-19
COVID-19急性后遗症导致长期味觉丧失的机制
- 批准号:
10554842 - 财政年份:2021
- 资助金额:
$ 71.4万 - 项目类别:
Mechanisms of inflammation-triggered taste loss and its recovery
炎症引发的味觉丧失及其恢复机制
- 批准号:
10599864 - 财政年份:2021
- 资助金额:
$ 71.4万 - 项目类别:
Sequence and Structure Specific DNA Binding by Cohesin and Genome Stability
粘连蛋白的序列和结构特异性 DNA 结合以及基因组稳定性
- 批准号:
10175465 - 财政年份:2018
- 资助金额:
$ 71.4万 - 项目类别:
Mechanisms of inflammation-triggered taste loss and its recovery
炎症引发的味觉丧失及其恢复机制
- 批准号:
9527911 - 财政年份:2017
- 资助金额:
$ 71.4万 - 项目类别:
HHcy-induced Inflammatory Monocyte and Macrophage Differentiation in Diabetes
HHcy 诱导的糖尿病炎症单核细胞和巨噬细胞分化
- 批准号:
8969420 - 财政年份:2015
- 资助金额:
$ 71.4万 - 项目类别:
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