The role of the Wnt5a/ROR2 in the pathogenesis of pulmonary arterial hypertension.
The role of the Wnt5a/ROR2 in the pathogenesis of pulmonary arterial hypertension.
批准号:
9167385
负责人:
VINICIO A DE JESUS PEREZ
金额:
$7.95万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-01 至 2018-08-31
关键词:
AdultAffectAutomobile DrivingBiologicalBiological AssayBlood VesselsCellsChemotactic FactorsChronicClinicalCoculture TechniquesCommunicationComplexDefectDevelopmentDiabetic RetinopathyDiseaseEndothelial CellsEventFailureFemale of child bearing ageGenesGoalsGrowthHeart failureHumanHypoxiaIndividualInjuryKnock-outKnockout MiceKnowledgeLifeLigandsLinkLungMeasuresMediatingMethodsMorphogenesisMusMutationNatural regenerationOutcomePathogenesisPathway interactionsPatientsPericytesPhosphorylationPlayProtein Tyrosine KinasePulmonary CirculationPulmonary HypertensionPulmonary artery structureRecoveryRecruitment ActivityResearch Project GrantsRoleSecondary toSerineSignal TransductionSmall Interfering RNAStrokeTamoxifenTechniquesThreonineTimeTissuesTubeUp-RegulationVascular DiseasesWorkangiogenesisbasecell motilityexome sequencingimprovedinsightknock-downmagnetic beadsmatrigelmouse modelnovelnovel therapeuticsplanar cell polaritypostnatalpressurepreventpulmonary arterial hypertensionreceptorresponseretinal angiogenesistreatment strategy
中文摘要
肺动脉高压(PAH)是一种与异常增高相关的危及生命的疾病
英文摘要
Pulmonary arterial hypertension (PAH) is a life-threatening disorder that is associated with abnormal increase
in pulmonary pressures resulting from progressive loss and impaired regeneration of pulmonary microvessels.
A key event in the formation of functional vascular networks is coating of vascular tubes with pericytes, highly
specialized mural cells that directly interact with endothelial cells to provide support and protection to newly
formed blood vessels. Many studies have attempted to elucidate the mechanisms behind the small vessel loss
in PAH by centering on the role of the pulmonary microvascular endothelial cells (PMVECs) but few studies to
date have explored the contribution of pericytes to the disease. Using a novel magnetic bead-based method
to isolate pericytes directly from human lungs we have found that, compared to pericytes isolated from healthy
individuals, PAH pericytes fail to migrate and associate with healthy PMVECs during vascular network
formation. The mechanism involved in the recruitment of pericytes to blood vessels is related to activation of
the Wnt/Planar cell polarity (PCP), a pathway involved in orchestrating cell motility and alignment during tissue
formation. Our preliminary studies have shown that PMVECs and pericytes demonstrate concomitant
upregulation of Wnt5a and ROR2 in co-culture arguing that this Wnt/PCP ligand-receptor pair is necessary for
establishment of endothelial-pericyte interactions during pulmonary angiogenesis. We propose that (1)
activation of Wnt/PCP is necessary for PMVECs and pericytes to organize into functional pulmonary
microvessels and (2) that mutations that reduce Wnt/PCP activity impair pulmonary vascular regeneration after
injury. We will use a novel mouse model of endothelial-specific Wnt5a knockout together with cell-based
angiogenesis assays and gene editing techniques to study the involvement of Wnt5a and ROR2 in the
establishment of endothelial-pericyte interaction during normal pulmonary angiogenesis and demonstrate for
the first time that dysregulation of these two genes can reduce the capacity of PAH pericytes to establish
proper endothelial-pericyte interactions. Our ultimate goal is to expand the knowledge of the biological
responses involved in pulmonary angiogenesis and contribute to current efforts to develop new treatment
strategies aimed at preventing and/or reversing small vessel loss in PAH.
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会议论文
The Wnt7a/ROR2 axis in the pathogenesis of pulmonary arterial hypertension
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批准号:10619368
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项目类别:
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资助金额:$7.17万
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财政年份:2022
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负责人:VINICIO A DE JESUS PEREZ
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A novel microfluidic platform to study exosome biology in PAH.
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依托单位:
A novel microfluidic platform to study exosome biology in PAH.
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批准号:10378161
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项目类别:
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资助金额:$19.68万
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财政年份:2021
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负责人:VINICIO A DE JESUS PEREZ
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依托单位:
Stanford Undergraduate URM Summer Cardiovascular Research Program
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批准号:10246191
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项目类别:
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资助金额:$10.68万
-
财政年份:2019
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负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
Stanford Undergraduate URM Summer Cardiovascular Research Program
-
批准号:10021034
-
项目类别:
-
资助金额:$10.24万
-
财政年份:2019
-
负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
Stanford Undergraduate URM Summer Cardiovascular Research Program
-
批准号:10471319
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项目类别:
-
资助金额:$10.24万
-
财政年份:2019
-
负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
Stanford Undergraduate URM Summer Cardiovascular Research Program
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批准号:10686866
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项目类别:
-
资助金额:$10.25万
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财政年份:2019
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负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
Endothelial-pericyte interactions in the pathogenesis of pulmonary arterial hypertension
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批准号:10522873
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项目类别:
-
资助金额:$73.28万
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财政年份:2017
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负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
Endothelial-pericyte interactions in the pathogenesis of pulmonary arterial hypertension
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批准号:10689249
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项目类别:
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资助金额:$70.79万
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财政年份:2017
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负责人:VINICIO A DE JESUS PEREZ
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依托单位:
The Wnt7a/ROR2 axis in the pathogenesis of pulmonary arterial hypertension
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批准号:10869189
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项目类别:
-
资助金额:$11.62万
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财政年份:2017
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负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
The Wnt7a/ROR2 axis in the pathogenesis of pulmonary arterial hypertension
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批准号:10609932
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项目类别:
-
资助金额:$53.6万
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财政年份:2017
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负责人:VINICIO A DE JESUS PEREZ
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依托单位:
The Wnt7a/ROR2 axis in the pathogenesis of pulmonary arterial hypertension
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批准号:10444951
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项目类别:
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资助金额:$57.71万
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财政年份:2017
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负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
The role of the Wnt/planar cell polarity pathway in pulmonary angiogenesis
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批准号:8384685
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项目类别:
-
资助金额:$13.32万
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财政年份:2012
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负责人:VINICIO A DE JESUS PEREZ
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依托单位:
The role of the Wnt/planar cell polarity pathway in pulmonary angiogenesis
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批准号:8514704
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项目类别:
-
资助金额:$13.32万
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财政年份:2012
-
负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
The role of the Wnt/planar cell polarity pathway in pulmonary angiogenesis
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批准号:8688333
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项目类别:
-
资助金额:$13.32万
-
财政年份:2012
-
负责人:VINICIO A DE JESUS PEREZ
-
依托单位:
海外基金