Chitin and chitinases in SARS-CoV-2 infection
Chitin and chitinases in SARS-CoV-2 infection
批准号:
10742004
负责人:
Steven Van Dyken
金额:
$19.46万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-06-01 至 2025-05-31
关键词:
2019-nCoVACE2AcuteAddressAffectAirAirborne Particulate MatterAntibodiesAreaAttenuatedBindingBiological MarkersCOVID-19COVID-19 mortalityCOVID-19 pandemicCOVID-19 severityCardiovascular DiseasesCessation of lifeChitinChitinaseChronicClinicalCoughingDataDepositionDiabetes MellitusDictyopteraDiseaseDisease OutcomeDisease ProgressionDyspneaElderlyEnvironmentEnvironmental ExposureEnvironmental Risk FactorEpithelial CellsEpitheliumExhibitsExposure toFeverFunctional disorderHealthHouse Dust Mite AllergensHousingHumanHypertensionImmune responseImpairmentInfectionInflammationInflammation MediatorsInflammatoryInhalationInjuryIntegration Host FactorsLinkLong-Term EffectsLungLung diseasesLung immune responseMediatingMoldsMolecularMusPathologicPathologyPathway interactionsPatientsPatternPhasePhysiologyPolymersPolysaccharidesPopulationPost-Acute Sequelae of SARS-CoV-2 InfectionProcessPulmonary FibrosisPulmonary PathologyRaceRecombinantsRecoveryReporterRespiratory DiseaseRespiratory FailureRiskRoleSARS-CoV-2 infectionSARS-CoV-2 pathogenesisSeveritiesSeverity of illnessTMPRSS2 geneTestingTherapeuticTranslationsUnited StatesViralViral Respiratory Tract InfectionVirus Diseasesage relatedairway epitheliumbiomarker identificationcytokine release syndromedemographicsenzyme therapyepithelial injuryethnic minority populationfibrotic lung diseasegain of functionglobal healthillness lengthimprovedinnovationloss of functionmortalitymouse modelnew therapeutic targetnovelnovel therapeutic interventionpandemic diseaseparticlepatient stratificationpost SARS-CoV-2 infectionpredictive markerreceptorresponserestorationsevere COVID-19therapeutic targettransgene expressiontreatment strategy
中文摘要
摘要
英文摘要
ABSTRACT
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and resultant coronavirus disease 2019
(COVID-19) has caused a global health crisis, surpassing 100 million infections in the United States. SARS-
CoV-2 infections range from asymptomatic to respiratory failure and death, and can result in an array of long-
term effects collectively referred to as post-acute sequelae of SARS-CoV-2 infection (PASC). The
pathobiological mechanisms and environmental factors underlying the intensity and duration of these effects
remain unclear, but a range of chronic lung impairments that resemble complications associated with age-related
pulmonary fibrosis have been documented in severe COVID-19, suggesting that environmental drivers
implicated in pulmonary fibrosis may also influence the course of SARS-CoV-2 infection and PASC. We have
identified the environmental constituent chitin as a candidate environmental driver of persistent SARS-CoV-2-
induced disease, consistent with its previously described role in pulmonary fibrosis. Our preliminary studies show
that chitin spontaneously accumulates in the lungs of SARS-CoV-2-infected mice, and is accompanied by
alterations in the expression patterns of the major lung chitinase, AMCase, suggesting that chitin-chitinase
interactions may contribute to SARS-CoV-2 pathogenesis. In comparison with wild-type (WT) controls, mice that
genetically lack AMCase exhibit exacerbated lung pathology after infection with SARS-CoV-2, implicating chitin
and chitinases in the pathologic sequelae that occur during the recovery phase. Thus, we hypothesize that
environmental chitin can drive COVID-19 severity, epithelial dysregulation, and disease persistence, and that
epithelial chitinases attenuate this process by degrading chitin. In this project, we leverage recently developed
mouse models of SARS-CoV-2 infection and chitin exposure to delineate a host-environmental interaction that
may contribute to persistent lung impairments following SARS-CoV-2 infection. We will test our hypothesis by
addressing two Aims: (1) determine the influence of environmental chitin on the severity and persistence of lung
pathology after SARS-CoV-2 infection, and (2) define the role of mammalian chitinases in SARS-CoV-2 infection
and persistent lung disease. Understanding how environmental chitin influences long-lasting pathologic
responses after SARS-CoV-2 infection may lead to the identification of new biomarkers and therapeutic targets
associated with differential disease outcomes in COVID-19 and PASC.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Targeting chitin in fibrotic lung disease
-
批准号:10133134
-
项目类别:
-
资助金额:$42.18万
-
财政年份:2020
-
负责人:Steven Van Dyken
-
依托单位:
Targeting chitin in fibrotic lung disease
-
批准号:10579959
-
项目类别:
-
资助金额:$42.18万
-
财政年份:2020
-
负责人:Steven Van Dyken
-
依托单位:
Targeting chitin in fibrotic lung disease
-
批准号:10364640
-
项目类别:
-
资助金额:$42.18万
-
财政年份:2020
-
负责人:Steven Van Dyken
-
依托单位:
国内基金
海外基金
登录
查看更多内容
ACE2/AGXT2信号轴在甲基异柳磷诱导斑马鱼神经发育异常过程中的作用机制研究
-
批准号:JCZRLH202600625
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
ACE2 Ser623磷酸化调控MED1促VSMCs功能损伤在移植血管重构中的作用及机制研究
-
批准号:2026JJ50619
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:翁春艳
-
依托单位:
新型蝙蝠MERS簇冠状病毒HKU5的ACE2细胞受体识别及其分子机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:
-
依托单位:
铁皮石斛通过肠道 ACE2 修复 Trp/GPR142 介
导“肠-胰岛 ”轴血糖调控功能的降糖机制研
究
-
批准号:Y24H280055
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:颜美秋
-
依托单位:
人类ACE2变构抑制剂的成药性及其抗广谱冠状病毒感染的机制研究
-
批准号:82330111
-
项目类别:重点项目
-
资助金额:220万元
-
批准年份:2023
-
负责人:刘刚
-
依托单位:
CAFs来源的外泌体负性调控ACE2促进肾透明细胞癌癌栓新辅助靶向耐药的机制研究
-
批准号:82373169
-
项目类别:面上项目
-
资助金额:49万元
-
批准年份:2023
-
负责人:顾良友
-
依托单位:
新型蝙蝠MERS簇冠状病毒HKU5的ACE2受体识别及细胞入侵机制研究
-
批准号:32300137
-
项目类别:青年科学基金项目
-
资助金额:30万元
-
批准年份:2023
-
负责人:陈静
-
依托单位:
基于外泌体miRNAs介导细胞通讯的大豆ACE2激活肽调控血管稳态机制研究
-
批准号:32302080
-
项目类别:青年科学基金项目
-
资助金额:30万元
-
批准年份:2023
-
负责人:宋田源
-
依托单位:
基于AT2/ACE2/Ang(1-7)/MAS轴调控心脏-血管-血液系统性重构演变规律研究心衰气虚血瘀证及其益气通脉活血化瘀治法生物学基础
-
批准号:82305216
-
项目类别:青年科学基金项目
-
资助金额:30万元
-
批准年份:2023
-
负责人:姚骏凯
-
依托单位:
感毒清经ACE2/Ang(1-7)/MasR信号通路抑制PM2.5诱导慢性气道炎症的机制:聚焦肺泡巨噬细胞极化与“胞葬”的表型串扰
-
批准号:82305171
-
项目类别:青年科学基金项目
-
资助金额:30万元
-
批准年份:2023
-
负责人:吴永灿
-
依托单位: