Molecular Regulation of Vascular Sprout Formation
血管芽形成的分子调控
基本信息
- 批准号:9159384
- 负责人:
- 金额:$ 60.43万
- 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
- 起止时间:2016-08-15 至 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAllelesAlternative SplicingAttenuatedBindingBiochemicalBiological AssayBiological ModelsBlindnessBlood VesselsCancer PatientCardiovascular systemCell Culture TechniquesComplexCorneaDefectDevelopmentDiseaseDissectionEmbryoEndocytosisEndothelial CellsEquilibriumEventExudative age-related macular degenerationFamilyFishesGene ExpressionGeneticGenetic TranscriptionGoalsGrowthGuanosineIn VitroIschemiaKDR geneKnowledgeLifeLinkMacular degenerationMalignant NeoplasmsMembraneMolecularMonomeric GTP-Binding ProteinsMusPathway interactionsPlayPositioning AttributeProcessProtein CProtein IsoformsProteinsRGS19 geneRNA SplicingRecoveryRegulationReporterReportingResearchResolutionRiskRoleSemaphorinsShapesSignal PathwaySignal TransductionSubstrate SpecificityTestingTherapeuticTransgenic OrganismsTreesVEGFA geneVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth FactorsVascular blood supplyVascularizationVisionWound HealingZebrafishangiogenesisbaseblood vessel developmentin vivoinnovationinsightinterestmRNA Stabilitymolecular targeted therapiesmutantnew therapeutic targetnovelnovel therapeuticsorgan regenerationprogramspublic health relevancereceptorresearch studytumorvasculogenesis
项目摘要
PROJECT SUMMARY/ABSTRACT
Sprouting angiogenesis, the formation of blood vessel sprouts, is essential for building the complex and
highly branched vascular tree required to sustain life. This process also plays pivotal roles in wound healing
and organ regeneration. In addition, too much, too little or otherwise abnormal sprout formation is associated
with many diseases. Thus, there is much interest in the therapeutic manipulation of sprouting angiogenesis.
However, to achieve this we must first dissect the molecular mechanisms that regulate this vital process. This
is precisely the overarching goal of this pioneering proposal, the first to address how the Vascular Endothelial
Growth Factor (VEGF) and Semaphorin-PlexinD1 (Sema-PlxnD1) pathways interact via three shared
molecular components and determine fundamental aspects of sprout formation, such as the abundance,
positioning and shape of vascular branches. The experiments described here exploit the complementary
advantages of the zebrafish and cultured endothelial cells as model systems for sprouting angiogenesis,
employ innovative fluorescent reporters of post-transcriptional gene expression and novel zebrafish mutants of
each of the three shared pathway components. By elucidating how VEGF and Sema-PlxnD1 interact the
present study will provide key insights into the molecular mechanisms that endothelial cells use to integrate
opposing inputs during sprout formation and suggest novel molecular targets for therapeutic manipulation of
this process. Such new therapies could help to preserve the sight of people at risk for blindness due to
excessive corneal vascularization (exudative macular degeneration), restore proper blood supply to those
suffering from ischemia and limit the growth and spread of tumors in many cancer patients by normalizing their
tumor vasculature.
项目总结/摘要
萌芽血管生成,即血管萌芽的形成,对于构建复合体和
维持生命所需的高度分枝的血管树。这一过程在伤口愈合中也起着关键作用
和器官再生此外,太多、太少或以其他方式异常的芽形成是相关的
有很多疾病。因此,有很多兴趣在治疗操作的萌芽血管生成。
然而,为了实现这一目标,我们必须首先剖析调节这一重要过程的分子机制。这
正是这一开创性提案的首要目标,第一个解决血管内皮细胞如何
生长因子(VEGF)和脑信号蛋白-丛蛋白D1(Sema-PlxnD 1)通路通过三个共享的
分子组成,并决定芽形成的基本方面,如丰度,
血管分支的位置和形状。这里描述的实验利用了互补的
斑马鱼和培养的内皮细胞作为萌芽血管生成的模型系统的优点,
采用创新的转录后基因表达的荧光报告基因,
这三个共享的途径组件中的每一个。通过阐明VEGF和Sema-PlxnD 1如何相互作用,
目前的研究将提供关键的见解的分子机制,内皮细胞用于整合
在芽形成过程中的相反输入,并提出了新的分子靶点,用于治疗操作,
这个过程这种新的疗法可以帮助那些由于以下原因而有失明风险的人保持视力。
过度的角膜血管化(渗出性黄斑变性),恢复适当的血液供应,
患有缺血并通过使其正常化来限制许多癌症患者肿瘤的生长和扩散
肿瘤脉管系统
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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Jesús Torres-Vázquez其他文献
Jesús Torres-Vázquez的其他文献
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{{ truncateString('Jesús Torres-Vázquez', 18)}}的其他基金
Mechanistic bases of vessel diameter regulation by Plexind1 - Resubmission
Plexind1 调节血管直径的机制基础 - 重新提交
- 批准号:
10522665 - 财政年份:2022
- 资助金额:
$ 60.43万 - 项目类别:
Mechanistic bases of vessel diameter regulation by Plexind1 - Resubmission
Plexind1 调节血管直径的机制基础 - 重新提交
- 批准号:
10662561 - 财政年份:2022
- 资助金额:
$ 60.43万 - 项目类别:
Regulation of brain angiogenesis by the tumor suppressor Reck
肿瘤抑制因子 Reck 对脑血管生成的调节
- 批准号:
9130431 - 财政年份:2015
- 资助金额:
$ 60.43万 - 项目类别:
Molecular and cellular mechanisms of vascular patterning by PlexinD1 signaling
PlexinD1 信号传导血管模式的分子和细胞机制
- 批准号:
8764521 - 财政年份:2013
- 资助金额:
$ 60.43万 - 项目类别:
Molecular and cellular mechanisms of vascular patterning by PlexinD1 signaling
PlexinD1 信号传导血管模式的分子和细胞机制
- 批准号:
7837548 - 财政年份:2009
- 资助金额:
$ 60.43万 - 项目类别:
Molecular and cellular mechanisms of vascular patterning by PlexinD1 signaling
PlexinD1 信号传导血管模式的分子和细胞机制
- 批准号:
7583387 - 财政年份:2008
- 资助金额:
$ 60.43万 - 项目类别:
Molecular and cellular mechanisms of vascular patterning by PlexinD1 signaling
PlexinD1 信号传导血管模式的分子和细胞机制
- 批准号:
7741688 - 财政年份:2008
- 资助金额:
$ 60.43万 - 项目类别:
Molecular and cellular mechanisms of vascular patterning by PlexinD1 signaling
PlexinD1 信号传导血管模式的分子和细胞机制
- 批准号:
7991785 - 财政年份:2008
- 资助金额:
$ 60.43万 - 项目类别:
Molecular and cellular mechanisms of vascular patterning by PlexinD1 signaling
PlexinD1 信号传导血管模式的分子和细胞机制
- 批准号:
8387036 - 财政年份:2008
- 资助金额:
$ 60.43万 - 项目类别:
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