Role of miR125 in pulmonary hypertension secondary to interstitial lung disease

miR125在间质性肺疾病继发性肺动脉高压中的作用

基本信息

  • 批准号:
    10524037
  • 负责人:
  • 金额:
    $ 47.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-12-01 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

Project Summary Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary vascular remodeling, and death. One of the most common forms of PH is secondary to interstitial lung disease (group 3.2) with a prevalence of about 30-40% in patients with pulmonary fibrosis (PF). PH development secondary to PF increases mortality about 3-fold as the combined disease is refractory to most therapies. The lack of effective therapies can be attributed, at least in part, to the lack of a relevant pre-clinical model of PF-PH. We have developed a novel pre-clinical rat model of combined PF-PH that recapitulates most of the pathophysiologic findings seen in patients with PF-PH. We have also identified a novel microRNA, miR125b-3p (miR125b), which is preferentially and significantly upregulated in the lungs of rats and humans with combined PF-PH compared to PF alone. miR125 upregulation is associated with significant downregulation of its target TNFAIP3 leading to increased expression of Slug, a transcription factor responsible for promoting endothelial to mesenchymal transition (EndMT). Our preliminary data shows overexpression of miR125b in the lungs of rat with pre-existing PF is sufficient to induce PH and to promote EndMT in human pulmonary artery endothelial cells (HPAECs) in vitro. The goal of this proposal is to determine how miR125 induces pulmonary vascular remodeling and EndMT to promote PH in pre-existing PF and to investigate the therapeutic potential of targeting miR125 and Snai2 in preventing PH in pre-existing PF. Our central hypotheses are: 1) marked increase of miR125b in the lungs promotes transition of PF to PF-PH by decreasing the expression of its target TNFAIP3 resulting in Snai2 upregulation that stimulates EndMT leading to worsening pulmonary vascular remodeling; and 2) Knock-down of miR125b and/or Slug in the lungs of rats with pre-existing PF prevents transition from PF to PF-PH. Aim 1 will gain mechanistic insights into the role of miR125b/Slug axis in promoting PH by driving vascular remodeling in rats/patients with pre-existing PF; Aim 2 will gain mechanistic insights into the role of miR125b/Slug axis in promoting PH by driving EndMT in rats/patients with pre-existing PF; and Aim 3 will examine whether miR125b and/or Slug can serve as novel therapeutic targets to prevent the transition of PF to PF-PH. The proposed studies will yield important insights into the mechanisms of miR125 overexpression induced PH, thus allowing us to target miR125 and/or Slug as novel therapeutic strategies to prevent PH.
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)

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 }}

Mansoureh Eghbali其他文献

Mansoureh Eghbali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('Mansoureh Eghbali', 18)}}的其他基金

Role of intestinal inflammation in oxidized lipid induced pulmonary hypertension
肠道炎症在氧化脂质诱导的肺动脉高压中的作用
  • 批准号:
    10381356
  • 财政年份:
    2022
  • 资助金额:
    $ 47.49万
  • 项目类别:
Role of Chromosome Y gene, Uty, in protecting against Pulmonary Hypertension
Y 染色体基因 Uty 在预防肺动脉高压中的作用
  • 批准号:
    10310983
  • 财政年份:
    2021
  • 资助金额:
    $ 47.49万
  • 项目类别:
Role of Chromosome Y gene, Uty, in protecting against Pulmonary Hypertension
Y 染色体基因 Uty 在预防肺动脉高压中的作用
  • 批准号:
    10454301
  • 财政年份:
    2021
  • 资助金额:
    $ 47.49万
  • 项目类别:
Role of miR125 in pulmonary hypertension secondary to interstitial lung disease
miR125在间质性肺疾病继发性肺动脉高压中的作用
  • 批准号:
    10312768
  • 财政年份:
    2019
  • 资助金额:
    $ 47.49万
  • 项目类别:
Role of miR125 in pulmonary hypertension secondary to interstitial lung disease
miR125在间质性肺疾病继发性肺动脉高压中的作用
  • 批准号:
    9917602
  • 财政年份:
    2019
  • 资助金额:
    $ 47.49万
  • 项目类别:
Role of miR125 in pulmonary hypertension secondary to interstitial lung disease
miR125在间质性肺疾病继发性肺动脉高压中的作用
  • 批准号:
    10063562
  • 财政年份:
    2019
  • 资助金额:
    $ 47.49万
  • 项目类别:
Role of miR193 in oxidized lipid induced pulmonary hypertension
miR193在氧化脂质诱导的肺动脉高压中的作用
  • 批准号:
    9330227
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
Role of miR193 in oxidized lipid induced pulmonary hypertension
miR193在氧化脂质诱导的肺动脉高压中的作用
  • 批准号:
    9107288
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
Cardiac KCNE2 (MIRP1) Regulation by Estrogen and Cardiac Stress
雌激素和心脏应激对心脏 KCNE2 (MIRP1) 的调节
  • 批准号:
    7842057
  • 财政年份:
    2009
  • 资助金额:
    $ 47.49万
  • 项目类别:
Cardiac KCNE2 (MIRP1) Regulation by Estrogen and Cardiac Stress
雌激素和心脏应激对心脏 KCNE2 (MIRP1) 的调节
  • 批准号:
    8094521
  • 财政年份:
    2008
  • 资助金额:
    $ 47.49万
  • 项目类别:

相似海外基金

Behaviour-based cell separation to interrogate host cell heterogeneity in CAR-T cell therapies
基于行为的细胞分离,以探究 CAR-T 细胞疗法中宿主细胞的异质性
  • 批准号:
    461308
  • 财政年份:
    2022
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Operating Grants
Microscopy-based cell separation, selective propagation, and selective single cell sequencing
基于显微镜的细胞分离、选择性增殖和选择性单细胞测序
  • 批准号:
    RGPIN-2020-05412
  • 财政年份:
    2022
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Discovery Grants Program - Individual
Microscopy-based cell separation, selective propagation, and selective single cell sequencing
基于显微镜的细胞分离、选择性增殖和选择性单细胞测序
  • 批准号:
    RGPIN-2020-05412
  • 财政年份:
    2021
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Discovery Grants Program - Individual
High throughput cell separation device
高通量细胞分离装置
  • 批准号:
    447860429
  • 财政年份:
    2020
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Major Research Instrumentation
Development of cell separation technology using a quadrupole capillary dielectrophoretic device
使用四极毛细管介电泳装置的细胞分离技术的开发
  • 批准号:
    20K04276
  • 财政年份:
    2020
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Microscopy-based cell separation, selective propagation, and selective single cell sequencing
基于显微镜的细胞分离、选择性增殖和选择性单细胞测序
  • 批准号:
    RGPIN-2020-05412
  • 财政年份:
    2020
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Discovery Grants Program - Individual
Collaborative Research: Towards High-Throughput Label-Free Circulating Tumor Cell Separation using 3D Deterministic Dielectrophoresis (D-Cubed)
合作研究:利用 3D 确定性介电泳 (D-Cubed) 实现高通量无标记循环肿瘤细胞分离
  • 批准号:
    1917295
  • 财政年份:
    2019
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Standard Grant
Wide-field microscope to support research programs in image cytometry and image-based cell separation
宽视场显微镜支持图像细胞计数和基于图像的细胞分离研究项目
  • 批准号:
    RTI-2020-00530
  • 财政年份:
    2019
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Research Tools and Instruments
Characterization of Magnetic Particle Performance in Cell Separation
细胞分离中磁性颗粒性能的表征
  • 批准号:
    523032-2018
  • 财政年份:
    2019
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Experience Awards (previously Industrial Undergraduate Student Research Awards)
Collaborative Research: RUI: Towards High-Throughput Label-Free Circulating Tumor Cell Separation using 3D Deterministic Dielectrophoresis (D-Cubed)
合作研究:RUI:使用 3D 确定性介电泳 (D-Cubed) 实现高通量无标记循环肿瘤细胞分离
  • 批准号:
    1917299
  • 财政年份:
    2019
  • 资助金额:
    $ 47.49万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了