Soluble mediators of relapse
复发的可溶性介质
基本信息
- 批准号:10396046
- 负责人:
- 金额:$ 52.73万
- 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:2021-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:ANGPTL4 geneAcuteAlbuminuriaAllelesAnimal Disease ModelsAntibodiesBALB/cJ MouseBindingBody SurfaceBuffaloesCRISPR/Cas technologyCell NucleusCell membraneCellsCommon ColdCommon Cold VirusCytokine ReceptorsDependenceDevelopmentDiseaseDissociationDown-RegulationEndothelial CellsEphrin-B1EventExclusionFocal Segmental GlomerulosclerosisGene ProteinsGenomicsGlucocorticoidsHistologyHodgkin DiseaseHumanIL-13Ralpha1Inbred BALB C MiceIndividualInfectionInjectionsIntercellular adhesion molecule 1Interferon Type IIInterferonsInterleukin 4 ReceptorInterleukin-10Interleukin-2Interleukin-6KidneyLinkMediatingMediator of activation proteinModelingMusMyristica fragransNasal EpitheliumNatural ImmunityNatureNuclearPatientsPharmaceutical PreparationsProcessProteinsProteinuriaRattusRecurrent diseaseRelapseRenal glomerular diseaseRhinitisRhinovirusSignal PathwayStimulusTNF geneTherapeuticToxic effectUntranslated RNAVariantZinc Fingersadaptive immune responseadaptive immunitycytokinecytokine release syndromedesignfactor Aglutamyl aminopeptidasein vivoinsertion/deletion mutationintravenous injectionmembermesangial cellnovelnovel strategiespodocytepreventreceptorsynergismtargeted treatmenttranscription factortreatment strategy
项目摘要
Abstract
The most common event preceding relapse of primary glomerular diseases like Minimal Change
Disease and Focal and Segmental Glomerulosclerosis is the common cold. Treatment of disease
relapse is a lengthy process involving glucocorticoids and other immunosuppressive medications, some
of which have multi-system toxicity. We hypothesized that relapse is induced by a “cytokine storm” that
follows infection by common cold viruses like Rhinovirus. A “cytokine cocktail” was designed around
the soluble Rhinovirus receptor and induces acute albuminuria after single intravenous injection in mice
with low podocyte Zhx2 expression, a common feature in MCD and FSGS patients. This cytokine
cocktail comprises of components of the innate and adaptive immune response that are necessary and
sufficient to induce acute albuminuria. Exclusion of any member from the cytokine cocktail, or injection
of individual members does not induce albuminuria.
In this proposal, we will develop therapeutic strategies to prevent relapse of glomerular diseases after
a common cold, by depleting soluble cytokines in the cytokine storm, or blocking their receptors in the
glomerulus.
In Aim 1, studies on cytokine depletion or receptor blockage in the podocyte will be conducted, and
receptor dependent and independent mechanisms identified.
In Aim 2, studies on cytokine depletion or receptor blockage in endothelial and mesangial cells will be
conducted, and receptor dependent and independent mechanisms identified.
In Aim 3, a therapeutic strategy that combines cytokine depletion with receptor blockage will be
developed.
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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Sumant Singh Chugh其他文献
Sumant Singh Chugh的其他文献
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{{ truncateString('Sumant Singh Chugh', 18)}}的其他基金
Investigation of non-HIV Collapsing Glomerulopathy
非 HIV 塌陷性肾小球病的调查
- 批准号:
9750079 - 财政年份:2016
- 资助金额:
$ 52.73万 - 项目类别:
Renal Protective Effects of Circulating Angiopoietin-like-4
循环血管生成素样 4 的肾脏保护作用
- 批准号:
8816097 - 财政年份:2014
- 资助金额:
$ 52.73万 - 项目类别:
Renal Protective Effects of Circulating Angiopoietin-like-4
循环血管生成素样 4 的肾脏保护作用
- 批准号:
9002042 - 财政年份:2014
- 资助金额:
$ 52.73万 - 项目类别:
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