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
- 批准号:10296535
- 负责人:
- 金额:$ 55.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAirway DiseaseAnti-Inflammatory AgentsAntioxidantsBasal CellBasal Cell HyperplasiaCDH1 geneCell Culture TechniquesCell CycleCell Differentiation processCell ProliferationCellsChronic Obstructive Airway DiseaseConsumptionDataDevelopmentDietEpithelialEpithelial CellsGenesGoblet CellsHOX proteinHealthHealth BenefitHomeobox GenesHomeostasisHumanImmune responseInfectionInjuryInnate Immune ResponseKnockout MiceLeadLungLung InflammationLung diseasesMaintenanceMetaplastic CellMetaplastic Squamous CellMolecularMorphogenesisMusNatural ImmunityNatural regenerationOutcomePathologicPathway interactionsPatientsPlacebosPlayPropertyPublishingQuercetinRegenerative pathwayRegulationRepressionResearchRespiratory Tract InfectionsRhinovirusRhinovirus infectionRoleSTC2 geneSignal TransductionSiteStructureTestingTissuesadaptive immune responseadaptive immunityairway epitheliumairway regenerationairway remodelingbasebronchial epitheliumchemokinecytokinedisease phenotypeepithelial repairepithelium regenerationimprovedinsightknock-downmouse modelnon-smokernovelpolarized cellpolyphenolpreventpulmonary functionrepairedresponsestem cellstranscriptional reprogrammingtranscriptomics
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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