Particulate matter-induced changes in DNA methylome and transcriptome

颗粒物诱导的 DNA 甲基化组和转录组变化

基本信息

  • 批准号:
    9098231
  • 负责人:
  • 金额:
    $ 62.85万
  • 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:
    2016-06-01 至 2020-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Particulate matter (PM) air pollution is a global environmental health problem that causes 3.7 million premature deaths annually, representing 6.7% of all deaths worldwide. These deaths are largely due to increased acute cardiopulmonary disease. Although efforts to abate PM levels led to reduction in PM-induced morbidity and mortality, the association between PM and cardiopulmonary disease still persists. There is need for early identification of individuals who are at risk for PM-induced cardiopulmonary disease to reduce the burden of disease further. Exposure to PM is associated with epigenetic modifications of DNA such as DNA methylation (5mC) and hydroxymethylation (5hmC) that regulate gene transcription. Assessment of these epigenetic changes may help with the identification of individuals at risk for development of PM-induced cardiopulmonary diseases. Increasing number of studies demonstrate that PM induces epigenetic changes but the implications of these findings are limited because these studies focused on the methylation patterns of the repetitive elements without detailed analysis of the whole genome. Furthermore, the studies were done in surrogate cells such as blood leukocytes and nasal epithelial cells without any correlation in target tissues. It is not known whether changes in DNA methylation or hydroxymethylation in peripheral blood monocytes can also be found in the target tissue or cell such as lung epithelial cells, alveolar macrophages or aortic endothelial cells. In preliminary studies, we found that PM treatment caused epigenetic changes characterized by reduction in 5mC and increased 5hmC in nasal and lung epithelial cells and alveolar macrophages. In addition to epigenetic changes, PM induced similar expression of some genes and differential expression of others in primary human nasal and lung epithelial cells ex vivo and in a murine model of PM exposure in vivo. PM-induced changes in gene expression and DNA methylation in primary human nasal epithelial cells were different among individuals as well as between males and females suggesting an important role for host-related factors such as genetics, age and sex in influencing the PM-induced responses. Based on our preliminary data, we hypothesized that changes in DNA methylation and hydroxymethylation and the gene expression (RNA-seq) in surrogate cells (nasal epithelial cells and peripheral blood mononuclear cells) can be used to predict those changes in target tissues (lung epithelial cells, and macrophages, heart and aorta). Using a clinically relevant murine model of PM exposure via inhalation, in Aim 1, we will determine the how PM-induced changes in DNA methylome and transcriptome differ in surrogate (nasal epithelium, and peripheral blood monocytes) and target cells (alveolar epithelial cells, macrophages, heart and aorta). In Aim 2, we will determine whether the host related factors (strain, sex and age) affect PM-induced changes in DNA methylome and transcriptome in surrogate and target cells and in Aim 3, we will determine whether the PM-induced changes in DNA methylome and transcriptome in surrogate and target cells persist throughout the lifespan.


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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Gokhan M. Mutlu其他文献

Laryngospasm and Paradoxical Bronchoconstriction After Repeated Doses of β<sub>2</sub>- Agonists Containing Edetate Disodium
  • DOI:
    10.4065/75.3.285
  • 发表时间:
    2000-03-01
  • 期刊:
  • 影响因子:
  • 作者:
    Gokhan M. Mutlu;Elizabeth Moonjelly;Lingtak Chan;Christopher O. Olopade
  • 通讯作者:
    Christopher O. Olopade

Gokhan M. Mutlu的其他文献

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{{ truncateString('Gokhan M. Mutlu', 18)}}的其他基金

Mechanisms Underlying Sympathetic Activation-dependent Endothelial Cell Activation by Chronic Intermittent Hypoxia
慢性间歇性缺氧导致交感神经激活依赖性内皮细胞激活的机制
  • 批准号:
    10612099
  • 财政年份:
    2019
  • 资助金额:
    $ 62.85万
  • 项目类别:
Mechanisms Underlying Sympathetic Activation-dependent Endothelial Cell Activation by Chronic Intermittent Hypoxia
慢性间歇性缺氧导致交感神经激活依赖性内皮细胞激活的机制
  • 批准号:
    10409555
  • 财政年份:
    2019
  • 资助金额:
    $ 62.85万
  • 项目类别:
CACHET - Pilot Project
CACHET - 试点项目
  • 批准号:
    10394646
  • 财政年份:
    2017
  • 资助金额:
    $ 62.85万
  • 项目类别:
CACHET - Pilot Project
CACHET - 试点项目
  • 批准号:
    10641985
  • 财政年份:
    2017
  • 资助金额:
    $ 62.85万
  • 项目类别:
Particulate matter-induced changes in DNA methylome and transcriptome
颗粒物诱导的 DNA 甲基化组和转录组变化
  • 批准号:
    9273532
  • 财政年份:
    2016
  • 资助金额:
    $ 62.85万
  • 项目类别:
Mechanisms of airborne particulate matter induced thrombosis
空气颗粒物诱发血栓形成的机制
  • 批准号:
    7921554
  • 财政年份:
    2006
  • 资助金额:
    $ 62.85万
  • 项目类别:
Mechanisms of airborne particulate matter induced thrombosis
空气颗粒物诱发血栓形成的机制
  • 批准号:
    7283020
  • 财政年份:
    2006
  • 资助金额:
    $ 62.85万
  • 项目类别:
Mechanisms of airborne particulate matter induced thrombosis
空气颗粒物诱发血栓形成的机制
  • 批准号:
    7488598
  • 财政年份:
    2006
  • 资助金额:
    $ 62.85万
  • 项目类别:
Role of alveolar macrophages in particulate matter-induced cardiopulmonary disease
肺泡巨噬细胞在颗粒物诱发的心肺疾病中的作用
  • 批准号:
    10163187
  • 财政年份:
    2006
  • 资助金额:
    $ 62.85万
  • 项目类别:
Role of alveolar macrophages in particulate matter-induced cardiopulmonary disease
肺泡巨噬细胞在颗粒物诱发的心肺疾病中的作用
  • 批准号:
    9764366
  • 财政年份:
    2006
  • 资助金额:
    $ 62.85万
  • 项目类别:

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