Role of MicroRNAs in Kidney Sodium Regulation

MicroRNA 在肾钠调节中的作用

• 批准号: 10401473
• 负责人: Michael B Butterworth
• 金额: $ 43.84万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-04 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10401473
• 关键词: Address; Adrenal Glands; Aldosterone; Angiotensin I; Angiotensin II; Angiotensinogen; Angiotensins; Atrial Fibrillation; Blood Pressure; Blood Pressure Monitors; Body Fluids; Cardiovascular system; Cell Line; Cells; Cortical Nephron; Data; Disease; Distal; Duct (organ) structure; Electrolyte Balance; Epithelial; Equilibrium; Feedback; Female; Glucocorticoids; Heart Hypertrophy; Homeostasis; Hormones; Hour; Hyperaldosteronism; Hypertension; Kidney; Knockout Mice; Link; Messenger RNA; Metabolic syndrome; MicroRNAs; Mineralocorticoid Receptor; Mineralocorticoids; Mus; Nature; Nephrons; Nucleotides; Phosphotransferases; Physiological; Premenopause; Production; Proteins; Regulation; Renin; Repression; Research Personnel; Resistant Hypertension; Risk; Role; Serum; Sex Differences; Signal Pathway; Signal Transduction; Signaling Protein; Sodium; System; Testing; Time; Untranslated RNA; Up-Regulation; Woman; arterial stiffness; base; blood pressure control; blood pressure elevation; blood pressure regulation; cardiovascular disorder risk; collecting tubule structure; coronary fibrosis; desensitization; dietary; dietary salt; in vivo; kidney cell; kidney fibrosis; male; mortality; mouse model; novel; osmotic minipump; protein expression; response; salt intake; sex; steroid hormone; stroke risk; tool

Project Summary/Abstract This proposal will investigate the role of small non‐coding RNAs, termed microRNAs (miRs), in the regulation of sodium (Na+) transport in the distal kidney nephron. We will investigate the hypothesis that the mineralocorticoid hormone, aldosterone regulates the expression of specific miR clusters in the distal kidney nephron cortical collecting duct (CCD). These miRs target mRNAs to alter Na+ transport. Expended up- regulation of the aldosterone-induced miRs then feedback to reduce the aldosterone response (negative feedback regulation). We propose to test this novel role of miRs in Na+ homeostasis but using a miR cluster KO mouse line. The miR-17~92 cluster will be deleted from the kidney nephron using a conditional, inducible KO line and the impact on long-term aldosterone signaling will be investigated. In the second part of the proposal, the mechanism the aldosterone-regulated miRs use to alter Na+ transport will be investigated in primary kidney cells.

项目总结/文摘