Investigation of endomucin as a novel regulator of angiogenesis

内粘蛋白作为血管生成的新型调节剂的研究

基本信息

  • 批准号:
    9238401
  • 负责人:
  • 金额:
    $ 49.25万
  • 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:
    2017-02-01 至 2020-01-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Angiogenesis, the growth of new blood vessels, is an important component of development, wound healing, and reproduction as well as a number of pathologies. Abnormal retinal angiogenesis leads to vision loss in a range of ocular pathologies including diabetic retinopathy, wet macular degeneration, and the retinopathy of prematurity. Endomucin (EMCN) is a mucin-like glycoprotein specifically expressed by endothelial cells of veins and capillaries. Our preliminary studies reveal a role for EMCN in the regulation of VEGF-induced endothelial functions in vitro and in normal angiogenesis in vivo. Reduction of EMCN expression using siRNA led to decreased VEGF-stimulated endothelial proliferation, migration and tube formation in vitro, and impaired retinal vascularization in vivo. This application proposes to test the hypothesis that EMCN plays a role in VEGF-induced pathologic neovascularization and that EMCN influences VEGF-stimulated functions by modulating its signaling. Studies are outlined to examine the role of EMCN in pathological angiogenesis using models of abnormal retinal and choroidal blood vessel growth as well as to understand the molecular mechanism that underlies EMCN's effects on VEGF-induced endothelial cell functions using in vitro systems. Studies in Aim 1 will examine the role of EMCN in the development of pathologic ocular neovascularization in vivo. The oxygen-induced model of retinal neovascularization and the laser-induced model of choroidal neovascularization will be utilized in conjunction with both gain and loss of function studies, using both siRNA and lentivirally-delivered shEMCN under the control of ICAM2, an endothelial-specific promoter, as well as adEMCN under the control of ICAM2. The effect of EMCN knockdown and overexpression on pathologic vessel growth will be quantified. Aim 2 proposes to elucidate the molecular mechanism of EMCN's role in the regulation of VEGF-induced endothelial functions. Studies using EMCN deletion mutants will be employed to determine if the effects of EMCN are mediated at the cell surface. The role of EMCN at the cell surface will be further investigated by examining its effect on VEGF binding and VEGFR2 stabilization/internalization. Intracellular effects will focus on a possible role of EMCN phosphorylation, the effect of EMCN on VEGFR2 phosphatase activity as well as the identification of potential EMCN intracellular binding partners. Results of these proposed studies will provide a better understanding of the role of EMCN in normal and pathologic angiogenesis and may lead to the development of novel endothelial cell-specific therapies for the suppression of vessel growth. !
摘要

项目成果

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Patricia Ann D'Amore其他文献

Patricia Ann D'Amore的其他文献

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{{ truncateString('Patricia Ann D'Amore', 18)}}的其他基金

Investigation of endomucin as a novel regulator of angiogenesis
内粘蛋白作为血管生成的新型调节剂的研究
  • 批准号:
    9414681
  • 财政年份:
    2017
  • 资助金额:
    $ 49.25万
  • 项目类别:
Investigation of endomucin as a novel regulator of angiogenesis
内粘蛋白作为血管生成的新型调节剂的研究
  • 批准号:
    10219259
  • 财政年份:
    2017
  • 资助金额:
    $ 49.25万
  • 项目类别:
Investigation of endomucin as a novel regulator of angiogenesis
内粘蛋白作为血管生成的新型调节剂的研究
  • 批准号:
    10456724
  • 财政年份:
    2017
  • 资助金额:
    $ 49.25万
  • 项目类别:
Fourth Biennial AMD Symposium
第四届AMD双年研讨会
  • 批准号:
    9193821
  • 财政年份:
    2016
  • 资助金额:
    $ 49.25万
  • 项目类别:
Third Biennial Symposium on Age Related Macular Degeneration
第三届年龄相关性黄斑变性双年研讨会
  • 批准号:
    8783667
  • 财政年份:
    2014
  • 资助金额:
    $ 49.25万
  • 项目类别:
Transmission Electron Microscope
透射电子显微镜
  • 批准号:
    8052990
  • 财政年份:
    2011
  • 资助金额:
    $ 49.25万
  • 项目类别:
Mechanisms That Mediate The Absence of Lymphatics in the Retina
调节视网膜淋巴管缺失的机制
  • 批准号:
    7458430
  • 财政年份:
    2008
  • 资助金额:
    $ 49.25万
  • 项目类别:
Mechanisms That Mediate The Absence of Lymphatics in the Retina
调节视网膜淋巴管缺失的机制
  • 批准号:
    7618416
  • 财政年份:
    2008
  • 资助金额:
    $ 49.25万
  • 项目类别:
Role of RPE-derived VEGF in Choroid Development and Stability
RPE 衍生的 VEGF 在脉络膜发育和稳定性中的作用
  • 批准号:
    7060810
  • 财政年份:
    2004
  • 资助金额:
    $ 49.25万
  • 项目类别:
Role of RPE-derived VEGF in Choroid Development and Stability
RPE 衍生的 VEGF 在脉络膜发育和稳定性中的作用
  • 批准号:
    8019446
  • 财政年份:
    2004
  • 资助金额:
    $ 49.25万
  • 项目类别:

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