The role of RNase L in kidney function
RNase L 在肾功能中的作用
基本信息
- 批准号:10730414
- 负责人:
- 金额:$ 44.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcute Renal Failure with Renal Papillary NecrosisAgeAgingApoptosisBasic ScienceBiochemicalBiological AssayBloodBody FluidsCell ExtractsCell ProliferationCellsCessation of lifeChronic Kidney FailureCisplatinDevelopmentDiseaseDisintegrinsElectrolytesEnvironmentEnzyme-Linked Immunosorbent AssayEnzymesEpidermal Growth FactorEpidermal Growth Factor ReceptorEvaluationExcretory functionExtracellular FluidFamilyFibroblastsFluid BalanceFolic AcidFunctional disorderGenesGlomerular Filtration RateGrowth and Development functionHomeostasisHumanInflammatoryInjuryInjury to KidneyInstitutionInterferonsIschemiaKidneyKnock-outKnockout MiceLigandsLinkMalignant NeoplasmsMediatingMembraneMetabolic acidosisMetalloproteasesMethodsMicroscopicMolecularMonitorMusNatural ImmunityNatural regenerationPI3K/AKTPathologicPathway interactionsPharmaceutical PreparationsPhysiologicalPhysiologyPlayPotassiumProductionProteinsReceptor ActivationRecoveryRegulationRenal functionRenal tubule structureResearchRibonucleasesRoleSignal PathwayStructureTestingTherapeuticTissuesTrainingTubular formationUremiaUrineVirusWestern BlottingWild Type Mousecell injurychemokinecytokineepidermal growth factor precursorhemodynamicshyperkalemiainjury and repairinsightinterstitialkidney cellkidney repairnephrogenesisnephrotoxicitynovelpreventreceptorrelease factorrenal damagerepairedundergraduate student
项目摘要
Acute kidney injury (AKI) is an abrupt loss of kidney function from various causes, which may lead
to several complications, including metabolic acidosis, hyperkalemia, uremia, increased
extracellular fluid volume, and death. Exogenous administration of epidermal growth factor (EGF)
has been found to enhance regeneration and repair renal tubule cells and accelerate the recovery
of renal function in post-ischemic and nephrotoxin-induced AKI. On the other hand, activation of
the EGF receptor (EGFR) also contributes to development and progression of chronic kidney
diseases (CKD). Clearly, the activation of EGF/EGFR plays an uncertain role, as it can be either
beneficial or detrimental to renal function after AKI. A better understanding of its regulation in the
kidney is, therefore, of importance. In this study, we hypothesize that RNase L is a very
important regulator in renal function, under basal circumstances, by permitting ADAM10-
dependent tubular EGF secretion, which regulates normal kidney development and growth.
In the context of AKI and tubular injury, these same pathways are essential for repair, but
need to be appropriately downregulated to prevent the transition of AKI to CKD. The
hypothesis is based on the results we recently obtained that 1) kidney size was significantly
reduced in RNase L knockout mice compared to wild-type mice, which was more pronounced
after aging; 2) urine EGF is completely abolished in RNase L knockout mice; 3) RNase L mediated
the expression and maturation of A Disintegrin and Metalloproteinase Domain 10 (ADAM10), a
transmembrane metalloprotease responsible for the shedding and releasing of the EGF precursor
in the kidney; and 4) RNase L knockout mice were recovered much faster than RNase L wild type
mice from folic acid (FA)-induced AKI through activation of the PI3K/AKT pathway. The specific
aims are to investigate the molecular mechanisms by which RNase L regulates the EGF excretion
in urine and the role of RNase L in kidney function under normal and pathological conditions and
explore whether RNase L is involved in AKI to CKD transition. Our study will provide novel insights
into how RNase L regulates the homeostasis of the EGF family of ligands and activation of the
receptors, which are vital in renal development, aging, physiology and pathophysiology. Most
importantly, the project will offer a unique opportunity for more undergraduate students
to be trained in the disease-related basic sciences.
急性肾损伤(Acute kidney injury, AKI)是一种由多种原因引起的肾脏功能的突然丧失
项目成果
期刊论文数量(0)
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AIMIN ZHOU其他文献
AIMIN ZHOU的其他文献
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{{ truncateString('AIMIN ZHOU', 18)}}的其他基金
The involvement of RNase L in the pathogenesis of inflammatory bowel disease
RNase L参与炎症性肠病发病机制
- 批准号:
8036416 - 财政年份:2011
- 资助金额:
$ 44.55万 - 项目类别:
The Role of RNase L in Cardiovascular Diseases
RNase L 在心血管疾病中的作用
- 批准号:
7060750 - 财政年份:2005
- 资助金额:
$ 44.55万 - 项目类别:
The Role of RNase L in Cardiovascular Diseases
RNase L 在心血管疾病中的作用
- 批准号:
6854416 - 财政年份:2005
- 资助金额:
$ 44.55万 - 项目类别:














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