Endothelial Barrier Function in Preeclampsia
先兆子痫的内皮屏障功能
基本信息
- 批准号:7741213
- 负责人:
- 金额:$ 21.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-08-24 至 2012-11-30
- 项目状态:已结题
- 来源:
- 关键词:AdhesionsAffectAntioxidantsApplications GrantsBlood capillariesCellsChymaseClinicalCoculture TechniquesCodeComplementary DNAComplexDiseaseEdemaEndothelial CellsEquilibriumEventExtravasationFocal Adhesion Kinase 1Functional disorderHumanInflammatoryIntercellular JunctionsKidneyKnowledgeMediatingMessenger RNAModelingModificationMolecularPAR-2 ReceptorPathogenesisPeptide HydrolasesPermeabilityPhenotypePlacentaPre-EclampsiaPregnancyPregnant WomenProductionProteinase-Activated ReceptorsProteinsProteinuriaRegulationResearch ProposalsRoleSeriesSignal TransductionSmall Interfering RNASpecificityStructureSystemTestingTight JunctionsVascular Endothelial Growth Factor ReceptorVascular Endothelial Growth FactorsVascular EndotheliumVascular PermeabilitiesVascular SystemWomanWorkbasecadherin 5capillarycell injuryinhibitor/antagonistinterstitialmRNA Expressionoccludinp21 activated kinaseprotein distributionprotein expressionrelease factorresearch studyresponsetrophoblast
项目摘要
Increased vascular permeability is an important component of endothelial dysfunction and a significant
pathophysiological event in preeclampsia (PE). In the original application of the research proposal
"Endothelial Barrier Function in Preeclampsia", a study of endothelial cells (ECs) derived from normal
pregnant women and from women with PE, we have found that disorganized EC junction protein vascular
endothelial (VE)-cadherin and tight junction protein occludin are the cellular basis of increased endothelial
permeability in PE. We further demonstrated that factors released from the placenta have the ability to
disrupt EC junction contacts and increase endothelial permeability. In an effort to identify candidate
molecules released from the placenta that induce an inflammatory phenotype in ECs during PE, we found
that placenta-derived chymotrypsin-like protease (CLP/chymase) exerts profound effects on vascular
endothelium. In our preliminary studies, we observed that CLP could disorganize endothelial junction protein
distribution and affect placenta soluble VEGF receptor-1 (sFlt-1) production. In this competing renewal grant
application, we will further explore the potential cellular and molecular mechanisms by which CLP regulates
EC barrier function in PE. Our central hypothesis is that placenta-derived CLPs mediate the increased
vascular permeability in PE by altering endothelial junction assembly and by increasing sFlt-1 release from
the placenta. We will test this hypothesis by experiments outlined under 3 specific aims: 1) to determine the
role of placental derived CLP in regulation of endothelial barrier function; 2) to elucidate to what extent the
placenta-derived protease-induced disassembly of endothelial adhesion/tight junctions is mediated by
proteinase-activated receptor (PAR) in PE; and 3) to explore whether enhanced trophoblast (TC) CLP
activity contributes to increased sFlt-1 release from the placenta in PE and what mechanisms are involved.
The proposed work will utilize TCs and ECs derived from normal and PE pregnancies. PAR siRNA will be
used to transfect ECs to study mechanisms underlying the placenta-derived CLP-induced disruption of EC
integrity that are relevant to PE. The influence of CLP on placental sFlt-1 will be studied. Results obtained
from the proposed work should enhance current knowledge of the role of the placenta and EC dysfunction in
the pathogenesis of PE.
增加的血管通透性是内皮功能障碍的重要组成部分,并且是一个重要的病理改变。
先兆子痫(PE)的病理生理事件。在最初的申请研究提案中,
“先兆子痫中的内皮屏障功能”,一项来自正常人的内皮细胞(EC)的研究
从孕妇和PE妇女,我们发现,紊乱的EC连接蛋白血管
内皮(VE)-钙粘蛋白和紧密连接蛋白occludin是内皮细胞增殖的细胞基础。
PE中的渗透性。我们进一步证明,胎盘释放的因子有能力
破坏EC连接接触并增加内皮渗透性。为了确定候选人
我们发现,在PE过程中,胎盘释放的分子诱导EC的炎症表型,
胎盘来源的糜蛋白酶样蛋白酶(CLP/糜蛋白酶)对血管生成有深远的影响,
内皮细胞在我们的初步研究中,我们观察到CLP可以破坏内皮连接蛋白,
分布并影响胎盘可溶性VEGF受体-1(sFlt-1)的产生。在这场竞争性的续约补助中
应用,我们将进一步探索CLP调节的潜在细胞和分子机制,
PE中EC屏障功能。我们的中心假设是胎盘来源的CLP介导了增加的
通过改变内皮连接组装和增加sFlt-1释放,
胎盘我们将通过3个具体目标下概述的实验来验证这一假设:1)确定
胎盘来源的CLP在调节内皮屏障功能中的作用; 2)阐明胎盘来源的CLP在多大程度上影响内皮屏障功能,
胎盘源性蛋白酶诱导的内皮细胞粘附/紧密连接的分解是由
蛋白酶激活受体(PAR)在PE;和3)探讨是否增强滋养层细胞(TC)CLP
活性有助于增加sFlt-1从PE中胎盘的释放,以及涉及的机制。
拟议的工作将利用来自正常和PE妊娠的TC和EC。PAR siRNA将被
用于检测EC,以研究胎盘来源的CLP诱导EC破坏的潜在机制
与PE相关的完整性。将研究CLP对胎盘sFlt-1的影响。获得的结果
从拟议的工作应该提高目前的知识的作用,胎盘和EC功能障碍,
PE的发病机制。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Preeclampsia Status Controls Interleukin-6 and Soluble IL-6 Receptor Release from Neutrophils and Endothelial Cells: Relevance to Increased Inflammatory Responses.
先兆子痫状态控制白介素6和可溶性IL-6受体从中性粒细胞和内皮细胞释放:与炎症反应增加有关。
- DOI:10.3390/pathophysiology28020013
- 发表时间:2021-04-08
- 期刊:
- 影响因子:0
- 作者:Wang Y;Gu Y;Alexander JS;Lewis DF
- 通讯作者:Lewis DF
Up-regulation of miR-203 expression induces endothelial inflammatory response: Potential role in preeclampsia.
miR-203 表达上调诱导内皮炎症反应:在先兆子痫中的潜在作用。
- DOI:10.1111/aji.12589
- 发表时间:2016-12
- 期刊:
- 影响因子:0
- 作者:Wang Y;Dong Q;Gu Y;Groome LJ
- 通讯作者:Groome LJ
Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells.
- DOI:10.1016/j.jsbmb.2013.11.017
- 发表时间:2014-03
- 期刊:
- 影响因子:4.1
- 作者:Zhong, Weijie;Gu, Baihan;Gu, Yang;Groome, Lynn J.;Sun, Jingxia;Wang, Yuping
- 通讯作者:Wang, Yuping
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
YUPING WANG其他文献
YUPING WANG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('YUPING WANG', 18)}}的其他基金
Spatiotemporal transcriptomics at the maternal-fetal interface in COVID placenta
新冠肺炎胎盘母胎界面的时空转录组学
- 批准号:
10440706 - 财政年份:2022
- 资助金额:
$ 21.98万 - 项目类别:
Spatiotemporal transcriptomics at the maternal-fetal interface in COVID placenta
新冠肺炎胎盘母胎界面的时空转录组学
- 批准号:
10618958 - 财政年份:2022
- 资助金额:
$ 21.98万 - 项目类别:
Mechanism of chymase activation in endothelial cells
内皮细胞食糜酶激活机制
- 批准号:
8636206 - 财政年份:2014
- 资助金额:
$ 21.98万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 21.98万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 21.98万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 21.98万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 21.98万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 21.98万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 21.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 21.98万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 21.98万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 21.98万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 21.98万 - 项目类别:
Grant-in-Aid for Early-Career Scientists