Regulation of TRAF2-Dependent Inflammatory Signaling by Small Proline Rich Protein 1A in the Myocardium
心肌中富含脯氨酸的小蛋白 1A 对 TRAF2 依赖性炎症信号的调节
基本信息
- 批准号:10375803
- 负责人:
- 金额:$ 4.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-07 至 2024-01-06
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAffectApoptosisAreaBinding SitesBiological AssayBloodBlood VesselsCardiacCardiac MyocytesCause of DeathCell DeathCell SurvivalCell membraneCellsCessation of lifeCharacteristicsChronicCicatrixCo-ImmunoprecipitationsComplexCoronaryCoronary arteryDataDiseaseEchocardiographyEtiologyExhibitsExposure toExtracellular MatrixFamilyFeedbackFibroblastsFibrosisFlow CytometryFunctional disorderGene ExpressionGene Expression ProfilingGenesGenetic TranscriptionHeartHeart failureHypertensionHypertrophyImmuneImmune responseImmunohistochemistryIn VitroInflammationInflammatoryInflammatory ResponseInjuryInvestigationIschemiaLabelLeft ventricular structureLigationLiteratureMusMyocardial InfarctionMyocardiumNecrosisObstructionPathologicPathologic ProcessesPathway interactionsPhasePhysiologyPlayPolymerase Chain ReactionProcessProtein FamilyProteinsPumpRegulationReportingResolutionResponse to stimulus physiologyRoleSPRR1ASignal PathwaySignal TransductionTNF Receptor-Associated FactorsTRAF2 geneTimeTroponin TTumor Necrosis Factor ReceptorTumor-infiltrating immune cellsUbiquitinUbiquitinationUp-RegulationWestern Blottingadeno-associated viral vectoradenoviral-mediatedcardiac repaircardioprotectioncytokinedifferential expressionexperienceexperimental studygenetic signaturehealingheart functionin vivoknock-downmembermulticatalytic endopeptidase complexnegative affectnoveloverexpressionpressureproline-rich proteinspromoterrecruitrepairedresponseresponse to injurytherapeutic developmenttranscriptome sequencingubiquitin-protein ligase
项目摘要
ABSTRACT:
Heart failure (HF) is a leading cause of death worldwide and defined by an inability of the heart to pump sufficient
blood throughout the body. HF can be induced by persistent conditions such as high blood pressure, or by acute
injuries such as myocardial infarction (MI). MI is characterized by the obstruction of a coronary blood vessel
resulting in ischemia. Cardiomyocytes (CMs) affected by the ischemia undergo necrosis and apoptosis. To clear
the resulting cellular debris, immune cells infiltrate the area while resident fibroblasts begin to secrete an
extracellular matrix-rich scar to maintain the structural integrity of the heart. This eloquent response is essential
to overcoming the initial injury, and exaggeration of any particular phase can have detrimental effects. While the
etiology of disease associated with high blood pressure and MI are unique, they share similar features such as
hypertrophy, inflammation, and fibrosis. To better understand the process of pathological cardiac remodeling,
we performed RNA-sequencing to identify transcriptional gene expression profiles associated with pathologic
fates. We identified a family of small proline-rich proteins (SPRRs) that are differentially regulated in disease;
Sprr1a is highly upregulated in response to inflammatory cytokines in CFs and CMs in the border zone (BZ) after
MI. Preliminary data suggests a predicted binding site between SPRR1A and tumor necrosis factor (TNF)
receptor associated factor (TRAF)2, an E3 ubiquitin ligase that acts in response to the TNF receptor at the
plasma membrane to propagate inflammatory signaling. Further investigation has led us to hypothesize that
SPRR1A is altering the ubiquitination status or proteasome function in CMs to halt pro-inflammatory signaling
and allow for the increase in inflammation-resolution pathways to occur. Separately, SPRR1A and TRAF2 may
also be playing a role in the rate of cell survival along the border of injury. Understanding the coordination of the
healing response following MI will build the basis needed for further therapeutic developments. This proposal
aims to determine the novel in vitro mechanism of action and associated in vivo complications associated with
the modulation of SPRR1A expression.
文摘:
项目成果
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Kimberly Nicole Burgos Villar其他文献
Kimberly Nicole Burgos Villar的其他文献
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{{ truncateString('Kimberly Nicole Burgos Villar', 18)}}的其他基金
Regulation of TRAF2-Dependent Inflammatory Signaling by Small Proline Rich Protein 1A in the Myocardium
心肌中富含脯氨酸的小蛋白 1A 对 TRAF2 依赖性炎症信号的调节
- 批准号:
10560492 - 财政年份:2022
- 资助金额:
$ 4.68万 - 项目类别:
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