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.

项目概要/摘要 该提案将研究小非编码 RNA（称为 microRNA (miR)）在调控中的作用 我们将研究以下假设： 盐皮质激素、醛固酮调节远端肾脏中特定 miR 簇的表达 这些 miR 靶向 mRNA 来改变 Na+ 转运。 醛固酮诱导的 miR 的调节然后反馈以减少醛固酮反应（负 我们建议使用 miR 簇来测试 miR 在 Na+ 稳态中的新作用。 使用条件诱导的方法将 miR-17~92 簇从肾单位中删除。 KO 线及其对长期醛固酮信号传导的影响将在第二部分进行研究。 提议，将研究醛固酮调节的 miR 用于改变 Na+ 转运的机制 原代肾细胞。