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.

慢性肾脏病 (CKD) 影响着 15% 的美国成年人30，而加压素是 与非糖尿病、糖尿病和多囊肾病 (PKD) 的进展相关1-18。 然而，加压素恶化肾病进展的具体机制 加压素是 164 个氨基酸前体的生物活性终产物。 目前认为前肽和生理产生仅限于大脑。 最近发现，在生理条件下，肾脏也会产生加压素，并且 PKD 在人类和小鼠中的表达均增加，因此，该项目的目的是 了解肾源性加压素对健康和健康的功能、调节和影响 我们有初步数据表明，缺乏肾源性加压素的小鼠 我们建议 (1) 确定其机制。 肾源性加压素通过其影响水平衡，以及 (2) 确定肾源性加压素是否 衍生的加压素参与了囊肿的生长和 PKD 的进展。 该项目将有助于阐明地方和地方之间相互作用的机制 全身加压素信号传导影响肾脏疾病，可能确定新的治疗方法 CKD 和 PKD 的目标和方法将在最大和最多的国家之一进行。 范德比尔特大学医学院内拥有世界各地科学多样化的肾脏病学部门 该项目已经获得了广泛的外部（哈罗德）中心医学部。 阿莫斯医学院发展奖 - 2020）和机构支持 财务支持和涉及内部和外部的全面职业发展计划 指导、研讨会和课程作业。