The Role of Nrf2 in Stabilizing the Epithelial Barrier in Particulate Matter Induced Rhinosinusitis
Nrf2 在稳定颗粒物诱发鼻窦炎的上皮屏障中的作用
基本信息
- 批准号:10320369
- 负责人:
- 金额:$ 40.94万
- 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:2019-01-04 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAdherens JunctionAffectAirAir PollutantsAir PollutionAmericanAnimal ModelAnimalsAnti-Inflammatory AgentsAntioxidantsBiological AssayCaringCell Culture TechniquesChronicComplementCongestiveCountyCritical PathwaysCytoskeletonDataDiseaseDown-RegulationEnhancersEnvironmental ExposureEpigenetic ProcessEpithelialEpithelial CellsExposure toFunctional disorderFundingGenesGenetic TranscriptionGenomicsHealthHealth Care CostsHost DefenseHumanHypersensitivityInflammationLeadLinkLiquid substanceMeasurementMediatingMedicalMentored Patient-Oriented Research Career Development AwardModelingModificationMolecularMorbidity - disease rateMucous MembraneMusMyosin ATPaseMyosin Light Chain KinaseNoseNuclearOxidative StressParticulateParticulate MatterPathogenesisPatient Self-ReportPatientsPermeabilityPhysiciansPlayPredispositionProcessProteinsProtocols documentationReactive Oxygen SpeciesRegulationResearch PersonnelRho-associated kinaseRoleScientistSecondary toSignal PathwaySinusSiteSymptomsSystemTestingTight JunctionsUltrafineUnited StatesUp-RegulationWorkaerosolizedbasechronic rhinosinusitisclinically relevanteffective therapyepigenomeepigenomicsin vivoinnovationmouse modelmultidisciplinarynoveloverexpressionpollutantpreservationpreventprogramspromoterrhinosinusitisrhosmall moleculesymptom treatmenttranscription factortranscriptome
项目摘要
Project Abstract
Chronic Rhinosinusitis (CRS) is a leading cause of morbidity globally with symptoms such as nasal congestion,
rhinorrhea, and discharge. It is the single most common self-reported chronic health condition and accounts for
billions of dollars in health care costs and lost work days annually. Exposure to air pollutants is thought to be a
critical modifier of CRS susceptibility. Despite marked reductions in air pollution levels in the United States, the
fine particulate component of air pollution [PM <2.5 (PM2.5)] and ultrafine pollutants secondary to traffic continue
to remain a recalcitrant issue in many counties in the United States. PM2.5 promotes oxidative stress and
inflammation in the mucosal lining of the nose and sinuses contributing to sinonasal epithelial barrier disruption.
As a physician-scientist, through my K23, I developed a strong rationale for the scientific premise of this proposal
to investigate the critical role of Nuclear related factor-2 (Nrf2) dependent host defense as a modifier of CRS.
As a new investigator, I am now in the process of transitioning from a K23 award to independent funding. My
preliminary studies have indicated that the transcription factor, Nrf2 is involved in the upregulation of an array of
anti-oxidant and anti-inflammatory gene programs involved in the preservation of epithelial integrity.
Furthermore, our preliminary results have indicated that chronic PM2.5 exposure causes suboptimal Nrf2 host
defense that may lead to CRS. Our central hypothesis in this proposal is that Nrf2 plays a critical role in
epithelial cell hypersensitivity to PM2.5 and modulation of epithelial barrier function in patients leading
to CRS. We have assembled a multidisciplinary team of experts and propose aims using mice and humans. In
SA1, we will test this hypothesis using a novel animal model of CRS, models of Nrf2 over-expression and
deficiency and state of the art in-vivo animal PM2.5 exposure system to mimic levels of PM2.5 relevant to humans.
We will also analyze expression of sinonasal epithelial tight junctional proteins. SA2 will determine the
mechanism by which PM induces epithelial barrier dysfunction and Nrf2 ameliorates this permeability using
human sinonasal epithelial cells and a novel PM2.5 cell culture exposure system. Lastly, SA3 will determine if
chronic PM2.5 exposure can cause epigenetic modifications in the sinonasal mucosa affecting Nrf2 transcription.
Our results will provide much needed translational data to target potential treatment targets in CRS and
contribute to our knowledge of this poorly understood disorder.
项目摘要
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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Murugappan Ramanathan其他文献
Murugappan Ramanathan的其他文献
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{{ truncateString('Murugappan Ramanathan', 18)}}的其他基金
Enhanced infectivity of SARS-CoV-2 in Particulate Matter exposed Sinonasal Epithelial Cells
暴露于颗粒物的鼻窦上皮细胞中 SARS-CoV-2 的感染性增强
- 批准号:
10169918 - 财政年份:2020
- 资助金额:
$ 40.94万 - 项目类别:
The Role of Nrf2 in Stabilizing the Epithelial Barrier in Particulate Matter Induced Rhinosinusitis
Nrf2 在稳定颗粒物诱发鼻窦炎的上皮屏障中的作用
- 批准号:
10077827 - 财政年份:2019
- 资助金额:
$ 40.94万 - 项目类别:
The Role of Nrf2 in Stabilizing the Epithelial Barrier in Particulate Matter Induced Rhinosinusitis
Nrf2 在稳定颗粒物诱发鼻窦炎的上皮屏障中的作用
- 批准号:
10532380 - 财政年份:2019
- 资助金额:
$ 40.94万 - 项目类别:
Role of the Indoor Environment on Oxidative Stress Related Sinonasal Inflammation
室内环境对氧化应激相关鼻窦炎症的作用
- 批准号:
8475599 - 财政年份:2011
- 资助金额:
$ 40.94万 - 项目类别:
Role of the Indoor Environment on Oxidative Stress Related Sinonasal Inflammation
室内环境对氧化应激相关鼻窦炎症的作用
- 批准号:
8651919 - 财政年份:2011
- 资助金额:
$ 40.94万 - 项目类别:
Role of the Indoor Environment on Oxidative Stress Related Sinonasal Inflammation
室内环境对氧化应激相关鼻窦炎症的作用
- 批准号:
8335447 - 财政年份:2011
- 资助金额:
$ 40.94万 - 项目类别:
Role of the Indoor Environment on Oxidative Stress Related Sinonasal Inflammation
室内环境对氧化应激相关鼻窦炎症的作用
- 批准号:
8224679 - 财政年份:2011
- 资助金额:
$ 40.94万 - 项目类别:
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