Lymphatics and lymphangiogenesis in kidney function and inflammation
肾功能和炎症中的淋巴管和淋巴管生成
基本信息
- 批准号:10087925
- 负责人:
- 金额:$ 44.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-23 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:Acute Renal Failure with Renal Papillary NecrosisAddressAffectAmericanAntigensBilateralBiological MarkersBiological ModelsBiologyCellsCharacteristicsChronicChronic Kidney FailureCisplatinClinicalClosure by clampDataDiabetes MellitusDiseaseDisease ProgressionEpidemicExcretory functionExhibitsFibrosisFunctional disorderFutureGeneticGenetic ModelsGenetic TechniquesGoalsHealthHealthcareHomeostasisHumanHypertensionImmuneImmune responseImpairmentInflammationInflammatoryInflammatory ResponseInjuryInjury to KidneyIschemiaKidneyKidney DiseasesKnowledgeLiquid substanceLymphangiogenesisLymphaticMedicareMetabolismMineralsMissionModelingMolecular GeneticsMorbidity - disease rateMusNational Institute of Diabetes and Digestive and Kidney DiseasesOsteoporosisOutcomePathogenesisPathologyPathway interactionsPatient-Focused OutcomesPatientsPharmacologyPhenotypePhysiologicalPhysiologyPositioning AttributePre-Clinical ModelProteinuriaPublic HealthPublishingRegulationRenal functionReperfusion InjuryReperfusion TherapyReportingResearchResistanceRiskRisk FactorsRoleRouteSeveritiesSodiumTestingTherapeuticTissuesUnited States National Institutes of HealthUp-RegulationVascular Endothelial Growth Factor CVascular Endothelial Growth Factor DVascular Endothelial Growth Factor Receptor-3Workanimal datachronic inflammatory diseasecytokinedensityhigh salt dietimprovedinjury recoveryinnovationinorganic phosphateinterstitialkidney preservationlymphatic vasculaturelymphatic vesselmacromoleculemortalitymouse modelnephrotoxicitynoveloverexpressionpressurepreventresponseresponse to injurysodium phosphatesolutestatisticssuccesstissue injury
项目摘要
PROJECT SUMMARY
Acute kidney injury (AKI) is a major cause of patient morbidity and mortality and appears to be a substantial risk
factor for future progression to chronic kidney disease (CKD). According to NIDDK statistics, roughly 14% of
Americans exhibit indications of CKD and 20% of all Medicare spending goes towards it management. Slowing
AKI-to-CKD progression, or identifying those patients most at risk for future CKD following AKI, is currently not
possible largely due to a fundamental gap in understanding of the pathogenesis of AKI-to-CKD transition.
Inflammation-associated lymphangiogenesis (LAG) is critical in regulating inflammation through fluid,
macromolecule (cytokines and antigens), and immune cell transport. While LAG has been identified in a host of
kidney diseases, reports have been mostly correlative. The long-term goal is to identify the mechanisms by
which lymphatics regulate tissue biology in chronic inflammatory disease. The overall objective in this
application is to identify the roles of the renal lymphatic vasculature during kidney injury and exploit the induction
of enhanced LAG as a potential therapy. The central hypothesis is that increasing renal lymphatics provides a
route of immune cell clearance while also potentially regulating solute transport. Guided by strong preliminary
data, this hypothesis will be tested by pursuing three specific aims: 1) Determine how renal LAG affects
inflammation and renal function in AKI; and 2) Determine the mechanisms by which renal LAG reduces AKI-to-
CKD progression; and 3) Determine the impact of enhancing renal lymphatic density on CKD. Under the first
aim, 3 models of AKI with diverse pathophysiologies will be used to identify how lymphatic density changes with
AKI and whether expanding lymphatics using KidVD mice, a genetic model of kidney-specific LAG, can limit the
AKI inflammatory response. Preliminary data suggest increased LAG protects against AKI. In the second aim,
how LAG alters the progression of AKI-to-CKD will be determined. Additionally, how changes in interstitial
pressures and mineral metabolism in the kidney with increased LAG during sodium and phosphate challenge
may provide a novel mechanism for AKI protection. For the third aim, therapeutic strategies to induce LAG once
CKD is established will be tested in each of the 3 renal pathologies. The proposed research is innovative, in the
applicant’s opinion, because it addresses and specifically targets the lymphatic vasculature of the kidney to
improve kidney function and inflammation upon AKI. New potential therapies and biomarkers are expected to
result from this work. The proposed research is significant because it is expected to identify previously unknown
mechanisms of kidney inflammatory regulation and transport functions. Ultimately, understanding the
mechanisms by which lymphatic vessels regulate kidney function and health has the potential to be
transformative to AKI response and treatment and in remediating the current epidemic of incurable chronic
kidney disease.
项目总结
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)
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Joseph Michael Rutkowski其他文献
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{{ truncateString('Joseph Michael Rutkowski', 18)}}的其他基金
Lymphatics and lymphangiogenesis in kidney function and inflammation
肾功能和炎症中的淋巴管和淋巴管生成
- 批准号:
10306392 - 财政年份:2020
- 资助金额:
$ 44.3万 - 项目类别:
Lymphatics and lymphangiogenesis in kidney function and inflammation
肾功能和炎症中的淋巴管和淋巴管生成
- 批准号:
10259635 - 财政年份:2020
- 资助金额:
$ 44.3万 - 项目类别:
Lymphatics and lymphangiogenesis in kidney function and inflammation
肾功能和炎症中的淋巴管和淋巴管生成
- 批准号:
10413663 - 财政年份:2020
- 资助金额:
$ 44.3万 - 项目类别:
Lymphatics and lymphangiogenesis in kidney function and inflammation
肾功能和炎症中的淋巴管和淋巴管生成
- 批准号:
10529283 - 财政年份:2020
- 资助金额:
$ 44.3万 - 项目类别:
Lymphatics and lymphangiogenesis in kidney function and inflammation
肾功能和炎症中的淋巴管和淋巴管生成
- 批准号:
10507856 - 财政年份:2020
- 资助金额:
$ 44.3万 - 项目类别:
Lymphatics and lymphangiogenesis in kidney function and inflammation
肾功能和炎症中的淋巴管和淋巴管生成
- 批准号:
9886866 - 财政年份:2020
- 资助金额:
$ 44.3万 - 项目类别:
Adiponectin transport: endothelial modulation of adipokine function
脂联素转运:脂肪因子功能的内皮调节
- 批准号:
8040911 - 财政年份:2010
- 资助金额:
$ 44.3万 - 项目类别:
Adiponectin transport: endothelial modulation of adipokine function
脂联素转运:脂肪因子功能的内皮调节
- 批准号:
7912521 - 财政年份:2010
- 资助金额:
$ 44.3万 - 项目类别:
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