Understanding the physiology and pathophysiology of kidney-derived vasopressin
Understanding the physiology and pathophysiology of kidney-derived vasopressin
批准号:
10644062
负责人:
Juan Pablo Arroyo Ornelas
金额:
$15.99万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-04-01 至 2028-03-31
关键词:
3-DimensionalAcademic Medical CentersAdultAffectAgeAmino AcidsAwardBlood PressureBrainCellsChronic Kidney FailureCystDataDevelopment PlansDiseaseDistalEducational workshopEquilibriumFinancial SupportFunctional disorderGrowthHealthHormonesHumanInstitutionKidneyKidney DiseasesMedical FacultyMedicineMentorshipMusNephrologyNephronsPhysiologicalPhysiologyPlayPolycystic Kidney DiseasesPopulationProductionRegulationRoleSignal TransductionTeacher Professional DevelopmentTransgenic MiceVasopressinsWaterWorkcareer developmentdiabeticmouse modelnew therapeutic targetnon-diabetic
中文摘要
慢性肾脏疾病(CKD)影响了15%的美国成年人30,抗利尿激素是其中之一
英文摘要
Chronic Kidney Disease (CKD) affects 15% of the US adult population30 and vasopressin is
associated with progression of non-diabetic, diabetic, and polycystic kidney disease (PKD). 1-18
However, the specific mechanism(s) through which vasopressin worsens progression of kidney
disease are unclear. Vasopressin is the biologically active end-product of a 164 amino acid pre-
pro-peptide and physiologic production is currently thought to be limited to the brain. We
recently found that vasopressin is also made in the kidney under physiologic conditions and
expression is increased in PKD in both humans and mice. Therefore, the aim of this project is to
understand the function, regulation, and impact of kidney-derived vasopressin in health and
disease. We have preliminary data that show that mice that lack kidney-derived vasopressin in
the distal nephron have altered water balance. We propose to (1) determine the mechanism
through which kidney-derived vasopressin influences water balance and (2) determine if kidney-
derived vasopressin is involved cyst growth and progression of PKD. Successful completion of
this project will help clarify the mechanism(s) through which the interplay between local and
systemic vasopressin signaling impacts kidney disease, potentially identifying new therapeutic
targets and approaches for CKD and PKD. Work will occur in one of the largest and most
scientifically diverse nephrology divisions in the world, within the Vanderbilt University Medical
Center Department of Medicine. This project has already received extensive external (Harold
Amos Medical Faculty Development Award – 2020) and institutional support in the form of
financial support and a comprehensive career development plan involving internal and external
mentorship, workshops, and coursework.
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