VEGF-C/VEGFR3 Regulation of VE-Cadherin in Sinusoidal Angiogenesis and Lymphangiogenesis

VEGF-C/VEGFR3 对 VE-钙粘蛋白在正弦血管生成和淋巴管生成中的调节

基本信息

  • 批准号:
    10563110
  • 负责人:
  • 金额:
    $ 3.41万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

Research Summary The blood, lymphatic, and sinusoidal vasculatures are molecularly and functionally distinct vascular networks whose normal growth and development are essential to support embryogenesis. While there has been notable effort to understand mechanisms of blood vessel development, relatively little is known about the role of vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3) and its main ligand VEGF-C in sinusoidal development. Despite decades of work on VEGFR2 and VEGFR3 signaling, insights into the field have been complicated by use of various genetic and pharmacologic models with divergent phenotypes. Furthermore, VEGF-C can weakly bind and activate VEGFR2 in addition to inducing VEGFR2-VEGFR3 heterodimers. As a result, the role of VEGF-C in vascular development remains incompletely understood. Therefore, our goal is to determine the role of VEGF-C/VEGFR3 in vascular development and identify novel signaling mechanisms through which it functions through a combination of in vivo mouse and in vitro cell culture studies. We and others have previously identified VEGF-C as an important regulator of fetal liver hematopoiesis. This was primarily attributed to defects in erythroid maturation, however the sinusoids are the only VEGFR3-positive cells in the fetal liver. Strikingly, endothelial deletion of VEGFR3 and vascular endothelial (VE-)cadherin gain- of-function mice both phenocopy VEGF-C knockout mice, suggesting that diminished fetal liver hematopoiesis is in fact due to sinusoidal defects. These mice also have decreased bone marrow (BM) sinusoids. BM defects due to endothelial loss of VEGFR3 are rescued by VE-cadherin haploinsufficiency, demonstrating that VEGFR3 negatively regulates VE-cadherin to promote sinusoidal growth. Whether this process depends on VEGF-C and the signaling mechanisms through which VEGFR3 regulates VE-cadherin remain unclear. Therefore, I hypothesize that VEGF-C activates VEGFR3 to directly and negatively regulate VE-cadherin during sinusoidal angiogenesis and lymphangiogenesis. Aim 1 will test whether haploinsufficiency of VE- cadherin can rescue fetal liver and lymphatic growth defects, as I have demonstrated to be true in the bone marrow sinusoids. Aim 2 will test whether VEGFR3 functions in a VEGF-C-dependent or independent manner in the skin, liver, and bone marrow during sinusoidal angiogenesis and lymphangiogenesis. Finally, Aim 3 will determine the mechanism by which VEGFR3 negatively regulates VE-cadherin through in vitro studies using human lymphatic endothelial cells. Together, these studies will bring novel insights into the mechanism by which VEGF-C/VEGFR3 may regulate VE-cadherin across various vascular beds in multiple organs, which could have important implications for liver regeneration, BM reconstitution, and lymphatic disorders.
研究总结

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ 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 }}

Derek C Sung其他文献

Derek C Sung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('Derek C Sung', 18)}}的其他基金

VEGF-C/VEGFR3 Regulation of VE-Cadherin in Sinusoidal Angiogenesis and Lymphangiogenesis
VEGF-C/VEGFR3 对 VE-钙粘蛋白在正弦血管生成和淋巴管生成中的调节
  • 批准号:
    10229242
  • 财政年份:
    2021
  • 资助金额:
    $ 3.41万
  • 项目类别:

相似国自然基金

帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
  • 批准号:
    32170319
  • 批准年份:
    2021
  • 资助金额:
    58.00 万元
  • 项目类别:
    面上项目
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
  • 批准号:
  • 批准年份:
    2021
  • 资助金额:
    58 万元
  • 项目类别:
ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究
  • 批准号:
    31672538
  • 批准年份:
    2016
  • 资助金额:
    62.0 万元
  • 项目类别:
    面上项目
番茄EIN3-binding F-box蛋白2超表达诱导单性结实和果实成熟异常的机制研究
  • 批准号:
    31372080
  • 批准年份:
    2013
  • 资助金额:
    80.0 万元
  • 项目类别:
    面上项目
P53 binding protein 1 调控乳腺癌进展转移及化疗敏感性的机制研究
  • 批准号:
    81172529
  • 批准年份:
    2011
  • 资助金额:
    58.0 万元
  • 项目类别:
    面上项目
DBP(Vitamin D Binding Protein)在多发性硬化中的作用和相关机制的蛋白质组学研究
  • 批准号:
    81070952
  • 批准年份:
    2010
  • 资助金额:
    35.0 万元
  • 项目类别:
    面上项目
研究EB1(End-Binding protein 1)的癌基因特性及作用机制
  • 批准号:
    30672361
  • 批准年份:
    2006
  • 资助金额:
    24.0 万元
  • 项目类别:
    面上项目

相似海外基金

Understanding the role of malaria red blood cell binding proteins in invasion and host specificity
了解疟疾红细胞结合蛋白在侵袭和宿主特异性中的作用
  • 批准号:
    2723209
  • 财政年份:
    2022
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Studentship
Focused ultrasound-mediated disruption of blood plasma protein binding with pharmacological molecules
聚焦超声介导破坏血浆蛋白与药理学分子的结合
  • 批准号:
    10046533
  • 财政年份:
    2020
  • 资助金额:
    $ 3.41万
  • 项目类别:
Contributions of Endothelial RNA-binding Protein Dysregulation to Blood Brain Barrier Defects and Neurodegenerative Disease
内皮 RNA 结合蛋白失调对血脑屏障缺陷和神经退行性疾病的影响
  • 批准号:
    10037854
  • 财政年份:
    2020
  • 资助金额:
    $ 3.41万
  • 项目类别:
Relationship between blood fatty acid-binding protein 4 and lipid metabolism induced by exercise
血脂肪酸结合蛋白4与运动诱导脂代谢的关系
  • 批准号:
    18K10838
  • 财政年份:
    2018
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding and modelling platelet flow and binding in blood
了解血液中的血小板流动和结合并对其进行建模
  • 批准号:
    LP160100786
  • 财政年份:
    2016
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Linkage Projects
Neutralizing the human Norovirus Histo-Blood Group Antigen Binding Pocket
中和人诺如病毒组织血型抗原结合袋
  • 批准号:
    286792586
  • 财政年份:
    2016
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Research Units
Study of brain-type fatty acid binding protein as a biomarker of psychiatric disorder for application to blood test
脑型脂肪酸结合蛋白作为精神疾病生物标志物应用于血液检测的研究
  • 批准号:
    16K19189
  • 财政年份:
    2016
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Development of the high blood pressure medical treatment by angiotensin receptor binding molecule
血管紧张素受体结合分子治疗高血压的研究进展
  • 批准号:
    24790950
  • 财政年份:
    2012
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Imaging study on receptor binding, cerebral blood flow and metabolism in diabates mouse brain
糖尿病小鼠脑受体结合、脑血流及代谢的影像学研究
  • 批准号:
    24591759
  • 财政年份:
    2012
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Elucidation of role of fatty acid-binding protein in vascular endothelial function and blood pressure control
阐明脂肪酸结合蛋白在血管内皮功能和血压控制中的作用
  • 批准号:
    23591106
  • 财政年份:
    2011
  • 资助金额:
    $ 3.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了