The role of NFkB in calcineurin inhibitor-induced renal fibrosis
NFkB 在钙调神经磷酸酶抑制剂诱导的肾纤维化中的作用
基本信息
- 批准号:10700842
- 负责人:
- 金额:$ 4.51万
- 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:2022-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AdvocateApplications GrantsAtopic DermatitisBiological AssayCalcineurinCalcineurin inhibitorCalmodulinCatalytic DomainCell SurvivalCell physiologyCommunicationComplexCritical ThinkingCyclosporineDataDevelopmentDrug ScreeningDrug toxicityEnd stage renal failureEventFibroblastsFibronectinsFibrosisFutureGenesGoalsImmune responseImmunityImmunosuppressionInflammatoryInjuryInjury to KidneyKidneyKidney FailureKidney TransplantationKnowledgeLupus NephritisMeasuresMediatingMediatorMethodsMolecularMorphologyMusNF-kappa BNF-kappaB-inducing kinaseNephrologyOrgan TransplantationOutcomePPP3CA genePathogenesisPathway interactionsPatient CarePatientsPersonsPharmaceutical PreparationsPharmacologic SubstancePharmacologyPhosphorylationPhosphotransferasesPhysiologyPlasmidsProcessProtein DephosphorylationProtein IsoformsProteinsRegulationRenal functionResearchResearch PersonnelRoleSignal PathwaySignal TransductionTacrolimusTestingTherapeuticTherapeutic immunosuppressionTissuesToxic effectTransforming Growth Factor betaUp-RegulationWorkWritingclinically relevantexperienceexperimental studyimprovedin vivoinhibitorinhibitor therapyinsightinterestinterstitialkidney cortexkidney dysfunctionkidney fibrosismutantnephrotoxicitynovelpharmacologicpost-transplantpreventrenal damageside effectskillssuccesstranscription factorvirtual
项目摘要
Project Abstract/Summary
Calcineurin inhibitors (CNIs) such as CsA and tacrolimus are vital immunosuppressive therapies in the
management of inflammatory conditions such as post-transplantation immunosuppression, lupus nephritis46 and
rare cases of atopic dermatitis47. Although CNIs have dramatically improved the quality of patient care, long-term
therapy causes irreversible damage to the kidneys in the form of renal fibrosis. These morphologic changes
ultimately lead to a decline in renal function and can progress to end-stage renal failure, a concern for both
clinicians and patients. Therefore, the molecular mechanisms by which CNIs induce kidney damage need to be
better understood, and to date, there are no specific therapeutic strategies to mitigate this injury.
There exists therefore, a critical need to explain mechanisms by which CNIs promote renal damage.
Interestingly, loss of CnAα activity in vivo increases markers of renal damage such as TGFβ and
fibronectin3. It is currently unknown which signaling mediators promote the expression of renal damage
markers upon loss of the CnAα isoform. Preliminary data show that exclusive loss of CnAα not only promotes
expression of renal profibrotic markers but also induces NFκB activation. However, the next question,
identifying whether these signaling changes occur via a common pathway, has not yet been answered. This
grant proposal will address this gap in knowledge and test the hypothesis that renal CnAα inhibition
upregulates NFκB signaling, which promotes irreversible renal damage. The expected project outcomes
will characterize CnAα’s role in mediating renal damage through its regulation of NFκB. These findings will
advocate and inspire future development of CnAα-sparing CNIs, ultimately circumventing the nephrotoxicity
noted with long-term CNI use.
To this end, this proposal seeks to I) determine whether NFκB activation promotes renal damage upon
CnAα inhibition and II) determine how renal CnAα inhibition drives NFκB signaling. Successful completion of the
proposed work will identify key mechanisms underlying the nephrotoxic effects of CNIs, thus informing future
development of CnAα-sparing CNIs and/or additional therapies to counter these toxic effects. The long-term goal
will be to mitigate the renal damage and dysfunction noted in patients placed on long-term CNI therapy.
项目摘要/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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Adaku Ume其他文献
Adaku Ume的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Adaku Ume', 18)}}的其他基金
The role of NFkB in calcineurin inhibitor-induced renal fibrosis
NFkB 在钙调神经磷酸酶抑制剂诱导的肾纤维化中的作用
- 批准号:
10463002 - 财政年份:2022
- 资助金额:
$ 4.51万 - 项目类别: