Understanding the physiology and pathophysiology of kidney-derived vasopressin

了解肾源性加压素的生理学和病理生理学

• 批准号: 10644062
• 负责人: Juan Pablo Arroyo Ornelas
• 金额: $ 15.99万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644062
• 关键词: 3-Dimensional; Academic Medical Centers; Adult; Affect; Age; Amino Acids; Award; Blood Pressure; Brain; Cells; Chronic Kidney Failure; Cyst; Data; Development Plans; Disease; Distal; Educational workshop; Equilibrium; Financial Support; Functional disorder; Growth; Health; Hormones; Human; Institution; Kidney; Kidney Diseases; Medical Faculty; Medicine; Mentorship; Mus; Nephrology; Nephrons; Physiological; Physiology; Play; Polycystic Kidney Diseases; Population; Production; Regulation; Role; Signal Transduction; Teacher Professional Development; Transgenic Mice; Vasopressins; Water; Work; career development; diabetic; mouse model; new therapeutic target; non-diabetic

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.

慢性肾脏疾病（CKD）影响美国成年人口的15％，加压素是 与非糖尿病，糖尿病和多囊性肾脏疾病（PKD）的进展有关。 1-18 但是，加压素使肾脏进展恶化的特定机制 疾病尚不清楚。加压素是164个氨基酸的生物活性终产物 促肽和生理生产目前被认为仅限于大脑。我们 最近发现，在生理条件下，加压素也是在肾脏中生产的 人类和小鼠的PKD中的表达均增加。因此，该项目的目的是 了解肾脏衍生的加压素在健康方面的功能，调节和影响 疾病。我们有初步数据表明，缺乏肾脏衍生的加压素的小鼠 远端肾脏改变了水平衡。我们建议（1）确定机制 通过哪些肾脏衍生的加压素影响水平的水平，（2）确定是否肾脏 衍生的加压素涉及PKD的囊肿生长和进展。成功完成 该项目将有助于阐明本地与本地之间的相互作用的机制 全身性加压素信号传导会影响肾脏疾病，有可能识别新疗法 CKD和PKD的目标和方法。工作将发生在最大，最大的之一 范德比尔特大学医学中，世界上科学多样化的肾脏科学分裂 中心医学系。这个项目已经收到了广泛的外部（哈罗德 AMOS医学教师发展奖 - 2020年）和机构支持 财政支持以及全面的职业发展计划涉及内部和外部 登陆，讲习班和课程。