Histologic and Transcriptional Profiling of Endothelial Cells During Progressive Pulmonary Fibrosis

进行性肺纤维化期间内皮细胞的组织学和转录谱

基本信息

  • 批准号:
    10616601
  • 负责人:
  • 金额:
    $ 8.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-05-01 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Idiopathic Pulmonary Fibrosis (IPF) is a progressive scarring lung disease that very often leads to respiratory failure. There remains a large unmet need for effective therapies. IPF is thought to be driven by injury to a vulnerable epithelium, sensitive to dysfunction either by genetic mutations or by the dose or type of injury. Epithelial dysfunction and senescence lead to diffuse tissue injury and activation of myofibroblasts. Dysregulated wound repair mechanisms may play a role in amplification of the tissue injury, tipping the balance from repair to fibrosis. Data is emerging that there are abnormalities in the pulmonary endothelium of patients who develop pulmonary fibrosis, although the cause/effect of these changes on the process of fibrogenesis is not well understood. Increased vascular permeability has been shown in the lungs of IPF patients and predicts mortality. In addition, several recent single-cell RNA sequencing studies have demonstrated loss of pulmonary capillaries and an increase in a bronchial vessel population. The full mechanistic implications of these changes have not been defined. Rho-associated kinase (ROCK) signaling has been shown to play a major role in several endothelial cell functions, including cell contractility and subsequent alterations in vascular permeability. I have shown in preliminary data that loss of ROCK2 specifically in endothelial cells in a mouse model (EC ROCK2 KO) prevents the development of pulmonary fibrosis induced by the delivery of intratracheal bleomycin. In addition to less pulmonary fibrosis, these mice had less vascular permeability in the early time period after bleomycin, before fibrosis develops. This finding suggests a link between endothelial ROCK2, vascular function, and pulmonary fibrosis, and hints at the potential for an opportunity for early intervention, when fibrosis may be preventable or reversible. In this current proposal, I propose to explore the protective phenotype in EC ROCK2 KO mice further by using these mice in a repetitive bleomycin model of pulmonary fibrosis, which has been shown to produce progressive fibrosis and is more similar to IPF. I will characterize the endothelial changes in this repetitive bleomycin model through staining and permeability assays. I will also perform single-cell RNA sequencing of mouse lungs with or without ROCK2, in the repetitive bleomycin model of pulmonary fibrosis. I will look for mechanistic links between endothelial ROCK2 and angiogenesis, senescence, endothelial to mesenchymal transition and apoptosis, all in the context of fibrogenesis.
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 }}

Rachel S Knipe其他文献

Rachel S Knipe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('Rachel S Knipe', 18)}}的其他基金

Loss of Endothelial S1PR1 Drives Post-Influenza Pulmonary Fibrosis
内皮 S1PR1 的缺失导致流感后肺纤维化
  • 批准号:
    10634045
  • 财政年份:
    2023
  • 资助金额:
    $ 8.33万
  • 项目类别:
Histologic and Transcriptional Profiling of Endothelial Cells During Progressive Pulmonary Fibrosis
进行性肺纤维化期间内皮细胞的组织学和转录谱
  • 批准号:
    10419046
  • 财政年份:
    2022
  • 资助金额:
    $ 8.33万
  • 项目类别:
Role and regulation of vascular permeability in pulmonary fibrosis
血管通透性在肺纤维化中的作用和调节
  • 批准号:
    9756465
  • 财政年份:
    2018
  • 资助金额:
    $ 8.33万
  • 项目类别:
Role and regulation of vascular permeability in pulmonary fibrosis
血管通透性在肺纤维化中的作用和调节
  • 批准号:
    10223415
  • 财政年份:
    2018
  • 资助金额:
    $ 8.33万
  • 项目类别:
Role and regulation of vascular permeability in pulmonary fibrosis
血管通透性在肺纤维化中的作用和调节
  • 批准号:
    10457937
  • 财政年份:
    2018
  • 资助金额:
    $ 8.33万
  • 项目类别:

相似海外基金

A novel motility system driven by two classes of bacterial actins MreB
由两类细菌肌动蛋白 MreB 驱动的新型运动系统
  • 批准号:
    22KJ2613
  • 财政年份:
    2023
  • 资助金额:
    $ 8.33万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
The structural basis of plasmid segregation by bacterial actins
细菌肌动蛋白分离质粒的结构基础
  • 批准号:
    342887
  • 财政年份:
    2016
  • 资助金额:
    $ 8.33万
  • 项目类别:
    Operating Grants
The structural basis for plasmid segregation by bacterial actins
细菌肌动蛋白分离质粒的结构基础
  • 批准号:
    278338
  • 财政年份:
    2013
  • 资助金额:
    $ 8.33万
  • 项目类别:
    Operating Grants
Cytoplasmic Actins in Maintenance of Muscle Mitochondria
细胞质肌动蛋白在维持肌肉线粒体中的作用
  • 批准号:
    8505938
  • 财政年份:
    2012
  • 资助金额:
    $ 8.33万
  • 项目类别:
Differential Expression of the Diverse Plant Actins
多种植物肌动蛋白的差异表达
  • 批准号:
    7931495
  • 财政年份:
    2009
  • 资助金额:
    $ 8.33万
  • 项目类别:
Studies on how actins and microtubules are coordinated and its relevancy.
研究肌动蛋白和微管如何协调及其相关性。
  • 批准号:
    19390048
  • 财政年份:
    2007
  • 资助金额:
    $ 8.33万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Suppression of Arabidopsis Reproductive Actins
拟南芥生殖肌动蛋白的抑制
  • 批准号:
    6655612
  • 财政年份:
    2003
  • 资助金额:
    $ 8.33万
  • 项目类别:
Suppression of Arabidopsis Reproductive Actins
拟南芥生殖肌动蛋白的抑制
  • 批准号:
    6546977
  • 财政年份:
    2003
  • 资助金额:
    $ 8.33万
  • 项目类别:
Interaction of myosin with monomeric actins
肌球蛋白与单体肌动蛋白的相互作用
  • 批准号:
    5311554
  • 财政年份:
    2001
  • 资助金额:
    $ 8.33万
  • 项目类别:
    Priority Programmes
STRUCTURE/INTERACTIONS OF ACTINS AND ACTIN-BINDING PROTEIN
肌动蛋白和肌动蛋白结合蛋白的结构/相互作用
  • 批准号:
    6316669
  • 财政年份:
    2000
  • 资助金额:
    $ 8.33万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了