Quercetin prevent airway epithelial remodeling and promote lung health in OPD

槲皮素可预防 OPD 患者气道上皮重塑并促进肺部健康

基本信息

项目摘要

PROJECT SUMMARY Patients with chronic obstructive pulmonary disease often show airway epithelial remodeling including basal cell hyperplasia, and goblet cell and squamous cell metaplasia. Such pathologic changes profoundly affect the outcome of respiratory infection as airway epithelium plays a crucial role in defining the innate and adaptive immunity in the lungs. Airway basal cells are the specialized stem cells and regenerate functional mucociliary- differentiated airway epithelium upon injury. The fact that COPD patients show airway epithelial remodeling indicate dysregulated repair mechanisms in airway basal cells. Our research suggests that quercetin, a natural polyphenol reverses airway epithelial remodeling in a mouse model of COPD. Our preliminary studies indicate that quercetin reprograms dysregulated repair pathways in COPD basal cells leading to regeneration of normal airway epithelium. We conducted transcriptomic analysis of airway basal cells from healthy non-smokers and COPD subjects and COPD basal cells treated with quercetin. Results from this microarray indicated dysregulation of genes involved in tissue development and epithelial differentiation in COPD cells. Intriguingly, the topmost differentially regulated genes in both these pathways are genes involved in lung morphogenesis HOXA1 and HOXB2. In normal basal cells, HOXA1 is highly expressed in basal cells, while HOXB2 expression increased at two weeks of culturing and correlated with polarization of cells, a prerequisite step in differentiation. COPD basal cells showed significantly reduced expression of both HOXA1 and HOXB2 and quercetin treatment increased expression of both genes. Based on these observations, we will examine a novel hypotheses that quercetin via modulation of HOXA1 and HOXB2 corrects the dysregulated repair mechanisms, thus improving immune responses to respiratory infections and lung function in COPD. In Specific Aim 1, we will determine the role of HOXA1 and HOXB2 in the regeneration of airway epithelium, and whether quercetin corrects the dysregulated repair mechanism in COPD by modulation of these HOX genes. In Specific Aim 2, we will examine the molecular mechanisms by which quercetin-induced HOXA1 and HOXB2 participates in the regeneration of airway epithelium. In Specific Aim 3, we will examine whether quercetin-induced HOXA1 and HOXB2 participate in limiting exaggerated innate immune responses to rhinovirus infection and prevent progression of lung disease in COPD. Finally, we will confirm whether quercetin treatment reduces airway epithelial remodeling in COPD patients and correlate with the expression of HOXA1 and HOXB2. Completion of these studies will provide important insight into airway epithelial regeneration and the mechanisms by which quercetin reduces airway epithelial remodeling in COPD.
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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Umadevi Sivanappa Sajjan其他文献

Umadevi Sivanappa Sajjan的其他文献

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{{ truncateString('Umadevi Sivanappa Sajjan', 18)}}的其他基金

Quercetin prevent airway epithelial remodeling and promote lung health in OPD
槲皮素可预防 OPD 患者气道上皮重塑并促进肺部健康
  • 批准号:
    10435564
  • 财政年份:
    2021
  • 资助金额:
    $ 55.37万
  • 项目类别:
Quercetin prevent airway epithelial remodeling and promote lung health in OPD
槲皮素可预防 OPD 患者气道上皮重塑并促进肺部健康
  • 批准号:
    10633252
  • 财政年份:
    2021
  • 资助金额:
    $ 55.37万
  • 项目类别:
Quercetin prevents progression of COPD lung disease by modulating Foxo3A activity
槲皮素通过调节 Foxo3A 活性预防 COPD 肺部疾病的进展
  • 批准号:
    8627791
  • 财政年份:
    2014
  • 资助金额:
    $ 55.37万
  • 项目类别:
Quercetin prevents progression of COPD lung disease by modulating Foxo3Aactivity
槲皮素通过调节 Foxo3A 活性预防 COPD 肺部疾病的进展
  • 批准号:
    9305694
  • 财政年份:
    2014
  • 资助金额:
    $ 55.37万
  • 项目类别:
Quercetin prevents progression of COPD lung disease by modulating Foxo3Aactivity
槲皮素通过调节 Foxo3A 活性预防 COPD 肺部疾病的进展
  • 批准号:
    9543962
  • 财政年份:
    2014
  • 资助金额:
    $ 55.37万
  • 项目类别:
Quercetin prevents progression of COPD lung disease by modulating Foxo3A activity
槲皮素通过调节 Foxo3A 活性预防 COPD 肺部疾病的进展
  • 批准号:
    8917098
  • 财政年份:
    2014
  • 资助金额:
    $ 55.37万
  • 项目类别:
Quercetin prevents progression of COPD lung disease by modulating Foxo3Aactivity
槲皮素通过调节 Foxo3A 活性预防 COPD 肺部疾病的进展
  • 批准号:
    9344531
  • 财政年份:
    2014
  • 资助金额:
    $ 55.37万
  • 项目类别:
Co-infections of rhinovirus and bacteria in chronic lung disorders
慢性肺部疾病中鼻病毒和细菌的双重感染
  • 批准号:
    7844968
  • 财政年份:
    2009
  • 资助金额:
    $ 55.37万
  • 项目类别:
Co-infections of rhinovirus and bacteria in chronic lung disorders
慢性肺部疾病中鼻病毒和细菌的双重感染
  • 批准号:
    7530219
  • 财政年份:
    2009
  • 资助金额:
    $ 55.37万
  • 项目类别:
Quercetin and Innate Immune Responses in COPD
槲皮素和慢性阻塞性肺病的先天免疫反应
  • 批准号:
    8103051
  • 财政年份:
    2008
  • 资助金额:
    $ 55.37万
  • 项目类别:

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气道疾病暴露组分析以解开哮喘疾病的决定因素 (EXPAND-Asthma) 中心
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