Poldip2: structural and functional implications for vascular disease

Poldip2:对血管疾病的结构和功能影响

基本信息

  • 批准号:
    9271231
  • 负责人:
  • 金额:
    $ 31.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-08-13 至
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Reactive oxygen species derived from NADPH oxidases and inflammation have been implicated in most vascular diseases, but also play a role in normal physiology and vascular healing via regulation of smooth muscle cell (SMC) proliferation and matrix secretion. Our laboratory has recently discovered a novel p22phox binding protein, polymerase delta interacting protein-2 (Poldip2), which regulates Nox4, polymerase-δ and cell cycle proteins and has important roles in growth, migration and collagen secretion. In this proposal, we test the hypothesis that the multiple roles of Poldip2 in vascular cells are a function of its binding partners, and that these functions can be specifically targeted using small interfering peptides. In Aim 1, we plan to characterize the physical interaction between Poldip2 and p22phox with the goal of defining peptides that can be used to specifically disrupt this interaction therapeutically. Truncation mutants and pulldown assays will be used to define interacting regions and to design peptides for cell and animal delivery. Aim 2 is devoted to using these peptides to determine the mechanism by which Poldip2 regulates extracellular collagen levels. We will test the hypothesis that depletion of Poldip2 reduces autophagy, thus enhancing collagen secretion. In Aim 3, we will determine the specific consequence of smooth muscle Poldip2-mediated matrix regulation on arterial stiffness and aneurysm formation using Poldipflox/flox animals crossed with smooth muscle-specific Cre mice in both chronic and acute settings, as well as hydrogel- or microparticle-mediated delivery of peptide decoys. Together, the experiments described in this proposal will not only extend our understanding of the vascular biology of Poldip2, but will allow us to take the first step towards translating our findings into a therapeutic modality potentially useful for treating vascular disease.
项目总结

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)

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Kathy K Griendling其他文献

364 - Role of βPIX in PDGF-Induced Lamellipodia Dynamics in VSMC
  • DOI:
    10.1016/j.freeradbiomed.2013.10.791
  • 发表时间:
    2013-11-01
  • 期刊:
  • 影响因子:
  • 作者:
    Charity Duran;Holly C Williams;Bernard Lassegue;Kathy K Griendling;Alejandra San Martin
  • 通讯作者:
    Alejandra San Martin

Kathy K Griendling的其他文献

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{{ truncateString('Kathy K Griendling', 18)}}的其他基金

Role of Poldip2 in endothelial barrier function and inflammation in the lung
Poldip2 在肺内皮屏障功能和炎症中的作用
  • 批准号:
    10266211
  • 财政年份:
    2020
  • 资助金额:
    $ 31.68万
  • 项目类别:
2010 Angiotensin Gordon Research Conference
2010年血管紧张素戈登研究会议
  • 批准号:
    7904440
  • 财政年份:
    2010
  • 资助金额:
    $ 31.68万
  • 项目类别:
NoxR1, a regulator of Nox4-dependent cytoskeletal remodeling in vascular cells
NoxR1,血管细胞中 Nox4 依赖性细胞骨架重塑的调节因子
  • 批准号:
    7731077
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:
Diverse Roles of Reactive Oxygen Species and Inflammation in Vascular Disease
活性氧和炎症在血管疾病中的多种作用
  • 批准号:
    8129768
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:
Opposing roles of Nox 1 and Nox 4 in vascular physiology and pathophysiology
Nox 1 和 Nox 4 在血管生理学和病理生理学中的相反作用
  • 批准号:
    7788447
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:
Vascular Oxidases in Migration
迁移中的血管氧化酶
  • 批准号:
    7822197
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:
Administrative Core A
行政核心A
  • 批准号:
    9271235
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:
Diverse Roles of Reactive Oxygen Species and Inflammation in Vascular Disease
活性氧和炎症在血管疾病中的多种作用
  • 批准号:
    8507552
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:
Diverse Roles of Reactive Oxygen Species and Inflammation in Vascular Disease
活性氧和炎症在血管疾病中的多种作用
  • 批准号:
    9236298
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:
Diverse Roles of Reactive Oxygen Species and Inflammation in Vascular Disease
活性氧和炎症在血管疾病中的多种作用
  • 批准号:
    7912906
  • 财政年份:
    2009
  • 资助金额:
    $ 31.68万
  • 项目类别:

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