Novel role of the lncRNA NEAT1 in smooth muscle phenotypic modulation

lncRNA NEAT1在平滑肌表型调节中的新作用

基本信息

  • 批准号:
    9251903
  • 负责人:
  • 金额:
    $ 38万
  • 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:
    2016-04-01 至 2020-02-28
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): The overall goal of the proposed research is to determine the previously unrecognized role of the (long non-coding RNA) lncRNA NEAT1 (nuclear paraspeckle assembly transcript 1) and its novel underlying mechanism in regulating the phenotypic switching of vascular smooth muscle cells (VSMCs). Many vascular diseases in humans, such as intimal hyperplasia post-angioplasty, are largely dependent upon VSMC phenotypic switching from a contractile to a "synthetic" phenotype that is associated with reduced smooth muscle-specific gene expression and increased cell proliferation and migration. Therefore, unraveling the mechanisms for the VSMC phenotypic switching is crucial for understanding the pathology of VSMC related vascular diseases and ultimately designing therapeutic agents for treatment. Emerging evidences demonstrate that lncRNAs represent a novel class of regulators for gene expression. In an effort to search for lncRNAs involved in the vascular injury, we conducted a large-scale lncRNA array screen using the rat carotid artery injured by a balloon denudation, a procedure resembling angioplasty in humans. This screen revealed that the lncRNA NEAT1 is induced in response to the arterial injury in vivo. Furthermore, expression of NEAT1 is also induced upon the stimulation of smooth muscle phenotypic modulation in vitro. Loss- and gain-of-function NEAT1 revealed that NEAT1 not only increases proliferation and migration of VSMCs but also decreases expression of smooth muscle-specific contractile proteins. Therefore, experiments described in this proposal will test the hypothesis that, the induction of NEAT1 plays a critical role in promoting smooth muscle phenotypic switching. In Aim 1, we will determine the role of NEAT1 in neointima hyperplasia following arterial injury. We will perform femoral artery wire injuries in the control and NEAT1 knock out mice and assess the effects of NEAT1 KO on the progression of neointima hyperplasia. In Aim 2, we will determine the mechanism by which NEAT1 abrogates smooth muscle-specific gene expression. Specifically we will evaluate the role of WDR5, a critical histone modifier for inducing an active form of chromatin, in mediating NEAT1 function in VSMCs. In Aim 3, we will determine the mechanism by which the transcription of NEAT1 is up-regulated upon the stimulation of smooth muscle phenotypic modulation by testing the role of an evolutionally conserved cAMP response element identified in the NEAT1 proximal promoter. Completion of these studies will provide novel insights into the mechanisms controlling smooth muscle phenotypic switching and determine if preventing the induction of NEAT1 may be an attractive therapeutic strategy for ameliorating occlusive vascular diseases.


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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Jiliang Zhou其他文献

Jiliang Zhou的其他文献

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{{ truncateString('Jiliang Zhou', 18)}}的其他基金

PIK3C3, a master regulator for smooth muscle identity
PIK3C3,平滑肌特性的主调节器
  • 批准号:
    10531615
  • 财政年份:
    2021
  • 资助金额:
    $ 38万
  • 项目类别:
PIK3C3, a master regulator for smooth muscle identity
PIK3C3,平滑肌特性的主调节器
  • 批准号:
    10367668
  • 财政年份:
    2021
  • 资助金额:
    $ 38万
  • 项目类别:
The novel smooth muscle-specific lncRNA CARMN is a critical regulator of smooth muscle phenotype
新型平滑肌特异性 lncRNA CARMN 是平滑肌表型的关键调节因子
  • 批准号:
    10543860
  • 财政年份:
    2020
  • 资助金额:
    $ 38万
  • 项目类别:
The novel smooth muscle-specific lncRNA CARMN is a critical regulator of smooth muscle phenotype
新型平滑肌特异性 lncRNA CARMN 是平滑肌表型的关键调节因子
  • 批准号:
    10327633
  • 财政年份:
    2020
  • 资助金额:
    $ 38万
  • 项目类别:
Role of Hippo-YAP Pathway in Smooth Muscle Phenotypic Modulation
Hippo-YAP 通路在平滑肌表型调节中的作用
  • 批准号:
    8600720
  • 财政年份:
    2012
  • 资助金额:
    $ 38万
  • 项目类别:
Role of Hippo-YAP Pathway in Smooth Muscle Phenotypic Modulation
Hippo-YAP 通路在平滑肌表型调节中的作用
  • 批准号:
    8991508
  • 财政年份:
    2012
  • 资助金额:
    $ 38万
  • 项目类别:
Role of Hippo-YAP Pathway in Smooth Muscle Phenotypic Modulation
Hippo-YAP 通路在平滑肌表型调节中的作用
  • 批准号:
    8403797
  • 财政年份:
    2012
  • 资助金额:
    $ 38万
  • 项目类别:
Role of Hippo-YAP Pathway in Smooth Muscle Phenotypic Modulation
Hippo-YAP 通路在平滑肌表型调节中的作用
  • 批准号:
    8246228
  • 财政年份:
    2012
  • 资助金额:
    $ 38万
  • 项目类别:

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