Regulation of minerals and fluids excretion in vitamin D

维生素 D 中矿物质和液体排泄的调节

• 批准号: 6768623
• 负责人: Yan Chun LI
• 金额: $ 12.46万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6768623
• 关键词: atrial natriuretic peptide; body fluid osmolarity; calbindin; calcium; dietary calcium; excretion; laboratory mouse; parathyroid hormones; renal tubular transport; sodium; tissue /cell culture; vitamin D; vitamin D deficiency; vitamin D receptors

DESCRIPTION (adapted from the application) Yan Chun Li, Ph.D., received a Ph.D. degree in biochemistry from Kent State University. After postdoctoral training at MIT and Harvard Medical School, he joined the University of Chicago as an Assistant Professor of Medicine. Dr. Li's long-term career goal is to develop into a leading independent investigator in the field of vitamin D research, with a long-term objective of understanding the physiological functions of the vitamin D endocrine system. As Dr. Li has no formal physiology training, the proposed five-year career development plan will allow him to receive extensive training on general physiology of the vitamin D endocrine system and the pathophysiology of vitamin D deficiency, particularly, in the area of vitamin D regulation of mineral metabolism. The sponsor of the present application, Dr. Brasitus, is an international authority on vitamin D signaling in normal and tumor cells. The Research Advisory Board, formed by Drs. Brasitus, Sitrin, Favus and Graves, is a group of internationally renowned physician-scientists with extensive research experience and expertise in the field of vitamin D research, and will provide collaboration and advice in Dr. Li's ongoing research. Dr. Li's research plan is to study the regulation of renal excretion of calcium, sodium and body fluid by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], using the vitamin D receptor (VDR) null mouse model. Studies will be focused on renal calbindin-D9k (CaBP-D9k), the rate-limiting protein involved in transcellular calcium transport, and atrial natriuretic peptide (ANP), a heart-derived hormone that promotes sodium and water excretion. The first aim is to study the effect of VDR inactivation, 1,25(OH)2-vitamin D deficiency, and dietary calcium on the expression of renal CaBP-D9k and its role in calcium reabsorption. The second aim is to study the regulation of renal CaBP-D9k expression by 1,25(OH)2D3, as well as the modulation of 1,25(OH)2D3-induced CaBP-D9k expression by PTH or calcium, using VDR(+/+) and (-/-) primary renal tubule cell cultures. This in vitro culture system will also be used to analyze the CaBP-D9k gene promoter and identify the vitamin D response element. The third goal is to study the effect of VDR inactivation on ANP expression and sodium and body fluid balance, in order to test in vivo, the hypothesis that 1,25(OH)2D3 negatively regulates ANP expression.

描述（改编自应用程序） 李艳春博士，获得博士学位。肯特州立大学生物化学学位 大学。在麻省理工学院和哈佛医学院进行博士后培训后，他 加入芝加哥大学担任医学助理教授。 李博士的长期职业目标是发展成为领先的独立专家 维生素 D 研究领域的研究员，长期目标是 了解维生素D内分泌系统的生理功能。作为 李医生没有受过正规的生理学训练，建议五年职业生涯 发展计划将使他能够接受广泛的一般培训 维生素 D 内分泌系统的生理学和维生素的病理生理学 D 缺乏，特别是在维生素 D 调节矿物质方面 代谢。本申请的发起人 Brasitus 博士是 正常细胞和肿瘤细胞中维生素 D 信号传导的国际权威。这 研究顾问委员会，由博士组成。 Brasitus、Sitrin、Favus 和 Graves 是 一群国际知名的医学科学家，拥有广泛的 维生素 D 研究领域的研究经验和专业知识，并将 为李博士正在进行的研究提供合作和建议。 李博士的研究计划是研究肾脏排泄的调节 1,25-二羟基维生素 D3 [1,25(OH)2D3] 中的钙、钠和体液，使用 维生素 D 受体 (VDR) 无效小鼠模型。研究将集中于肾脏 钙结合蛋白-D9k (CaBP-D9k)，参与跨细胞转运的限速蛋白 钙转运和心房钠尿肽（ANP），一种来自心脏的物质 促进钠和水排泄的激素。第一个目标是研究 VDR 失活、1,25(OH)2-维生素 D 缺乏和膳食钙的影响 肾CaBP-D9k表达及其在钙重吸收中的作用这 第二个目的是研究肾脏 CaBP-D9k 表达的调节 1,25(OH)2D3，以及 1,25(OH)2D3 诱导的 CaBP-D9k 的调节 使用 VDR(+/+) 和 (-/-) 原代肾小管通过 PTH 或钙表达 细胞培养物。该体外培养系统也将用于分析 CaBP-D9k 基因启动子并鉴定维生素 D 反应元件。第三个 目的是研究 VDR 失活对 ANP 表达和钠的影响 和体液平衡，为了在体内测试，假设 1,25(OH)2D3 负向调节 ANP 表达。