Role of CLIC5 in Podocyte Injury and Remodeling
CLIC5 在足细胞损伤和重塑中的作用
基本信息
- 批准号:8770472
- 负责人:
- 金额:$ 7.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-28 至 2016-06-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAdherenceAdhesionsAdriamycin PFSAdultAnimal ModelApicalArchitectureBasement membraneBiochemicalBiologicalBiological MarkersBiotinylationCell DeathCell FractionationCell LineCell membraneCell surfaceCellsCessation of lifeChloride ChannelsChloride IonChloridesChronic Kidney FailureClinicalComplexDataDiseaseDisease ProgressionFamilyFocal Segmental GlomerulosclerosisFoot ProcessFoundationsFunctional disorderGeneticGenetic PolymorphismGoalsHair CellsHumanImmunofluorescence MicroscopyIn VitroInjuryIntegral Membrane ProteinInterventionKidney DiseasesLaboratoriesLengthLifeLiteratureLiving DonorsMaintenanceMeasuresMediatingMediator of activation proteinMembrane ProteinsMembranous GlomerulonephritisMessenger RNAMethodsModelingMolecularMorphogenesisMusNPHS2 proteinNatural regenerationPathogenesisPatientsPeriodic acid Schiff stain methodPreventionProcessProteinsProteinuriaPublic HealthRecoveryRenal glomerular diseaseRoleSamplingSialic AcidsSignal PathwaySignal TransductionStagingStereociliumStructureTestingTherapeuticUrineVariantapical membranebasecell injurycellular imagingdensitydesignexperienceezringlomerular basement membraneglomerular filtrationin vivolight microscopynovelpodocalyxinpodocyteprotein expressionpublic health relevancerepairedresearch studyresponseresponse to injurysialylationtooltrafficking
项目摘要
DESCRIPTION (provided by applicant): In many glomerular diseases, proteinuria and disease progression are associated with podocyte loss by death or detachment. Understanding the mechanisms by which the podocyte maintains attachment and recovers by remodeling its large and foot processes after injury is critical for the identification of potential therapeutic targetsof glomerular diseases. Podocalyxin is an apical membrane protein that is required for the formation of podocyte large and foot processes. A decrease in the sialylation and expression of podocalyxin are associated with glomerular diseases. Chloride intracellular channel 5 (CLIC5) is an apical membrane protein that associates with podocalyxin and ezrin, and is an important intermediate adapter between the cell membrane and the cytoskeletal network. We have recently discovered that CLIC5-deficient podocytes display foot process effacement and a decrease in podocalyxin protein expression. CLIC5 protein expression is decreased in Minimal Change Disease compared with normal human living donors. Our long term goal is to identify and understand the proteins and signaling pathways necessary for podocyte survival and remodeling in response to glomerular injury. The aims of this proposal are twofold. First, we will determine the extent to which CLIC5 controls the proper trafficking and stability of podocalyxin in podocyte processes. Second, we will identify the role of CLIC5 in maintaining podocyte adhesion in response to glomerular injury in vivo. This project is significant because we will demonstrate a novel mechanism that is critical for podocyte recovery from injury. A combination of biochemical and cell biological approaches will be employed in cultured Clic5-deficient podocytes and Clic5-deficient mice. We expect to identify CLIC5 as a protein critical for podocytes to recover by maintaining their adherence to the glomerular matrix and to remodel their foot processes to reestablish the glomerular filtration barrier. The results of these experiments may aid in establishing a foundation for the rational design of effective clinical interventions for glomerular diseases.
描述(由申请人提供):在许多肾小球疾病中,蛋白尿和疾病进展与足细胞死亡或脱落造成的足细胞损失相关。了解足细胞在损伤后通过重塑其大突和足突来维持附着和恢复的机制对于识别肾小球疾病的潜在治疗靶点至关重要。足糖萼蛋白是足细胞大突和足突形成所需的顶端膜蛋白。足糖萼蛋白的唾液酸化和表达减少与肾小球疾病相关。氯离子胞内通道5(CLIC 5)是与足糖萼蛋白和埃兹蛋白缔合的顶端膜蛋白,并且是细胞膜和细胞骨架网络之间的重要中间衔接子。我们最近发现,CLIC 5缺陷足细胞显示足突消失和podocalyxin蛋白表达减少。与正常人活体供体相比,微小病变疾病中CLIC 5蛋白表达降低。我们的长期目标是识别和理解肾小球损伤后足细胞存活和重塑所必需的蛋白质和信号通路。这项建议有两个目的。首先,我们将确定CLIC 5控制足细胞过程中足糖萼蛋白的适当运输和稳定性的程度。其次,我们将确定CLIC 5在维持足细胞粘附中的作用,以响应体内肾小球损伤。这个项目是重要的,因为我们将证明一个新的机制,是足细胞从损伤中恢复的关键。将在培养的Clic 5缺陷足细胞和Clic 5缺陷小鼠中采用生物化学和细胞生物学方法的组合。我们期望将CLIC 5鉴定为足细胞通过维持其对肾小球基质的粘附而恢复的关键蛋白,并重塑其足突以重建肾小球滤过屏障。这些实验的结果可能有助于建立一个基础,合理设计有效的临床干预肾小球疾病。
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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Cynthia Tsui其他文献
Cynthia Tsui的其他文献
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{{ truncateString('Cynthia Tsui', 18)}}的其他基金
Role of CLIC5 in Podocyte Injury and Remodeling
CLIC5 在足细胞损伤和重塑中的作用
- 批准号:
8898791 - 财政年份:2014
- 资助金额:
$ 7.78万 - 项目类别:
GDNF and Ret are critical for glomerular development, maintenance, and protection
GDNF 和 Ret 对于肾小球发育、维持和保护至关重要
- 批准号:
7934535 - 财政年份:2009
- 资助金额:
$ 7.78万 - 项目类别:
GDNF and Ret are critical for glomerular development, maintenance, and protection
GDNF 和 Ret 对于肾小球发育、维持和保护至关重要
- 批准号:
8142009 - 财政年份:2009
- 资助金额:
$ 7.78万 - 项目类别:
GDNF and Ret are critical for glomerular development, maintenance, and protection
GDNF 和 Ret 对于肾小球的发育、维持和保护至关重要
- 批准号:
8536263 - 财政年份:2009
- 资助金额:
$ 7.78万 - 项目类别:
GDNF and Ret are critical for glomerular development, maintenance, and protection
GDNF 和 Ret 对于肾小球发育、维持和保护至关重要
- 批准号:
7707424 - 财政年份:2009
- 资助金额:
$ 7.78万 - 项目类别:
GDNF and Ret are critical for glomerular development, maintenance, and protection
GDNF 和 Ret 对于肾小球发育、维持和保护至关重要
- 批准号:
8320981 - 财政年份:2009
- 资助金额:
$ 7.78万 - 项目类别:
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