Role of microRNAs in kidney sodium regulation

microRNA 在肾脏钠调节中的作用

• 批准号: 8884812
• 负责人: Michael B Butterworth
• 金额: $ 34.65万
• 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: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8884812
• 关键词: Address; Adrenal Cortex Hormones; Aldosterone; Aldosterone Synthase; Angiotensin II; Area; Cells; Collaborations; Collecting Cell; Cortical Nephron; Development; Diet; Disease; Distal; Duct (organ) structure; Electrolytes; Epithelial; Epithelium; Equilibrium; Family; Future; Genomics; Homeostasis; Hormonal; Hormones; Hypertension; Hypoaldosteronism; Hypotension; Intervention; Kidney; Kidney Diseases; Knock-out; Knockout Mice; Link; Mediating; Mediator of activation protein; MicroRNAs; Mineralocorticoid Receptor; Mineralocorticoids; Modeling; Mus; Nephrons; Pathway interactions; Phosphorylation; Physiology; Positioning Attribute; Potassium; Proteins; Recycling; Regulation; Regulatory Pathway; Reporting; Role; Scaffolding Protein; Signal Pathway; Signal Transduction; Sodium; Sodium Channel; Sodium Chloride; Syndrome; Testing; Transgenic Organisms; Untranslated RNA; Work; epithelial Na+ channel; human disease; in vivo; intersectin 1; mouse model; novel; public health relevance; response; trafficking; uptake

 DESCRIPTION (provided by applicant): 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), to alter Na+ transport by targeting the expression of the scaffold protein intersectin-2. Using in vivo mouse models we will establish the regulation of miRs in the principal cells of the CCD. The significantly regulated miRs that are altered by aldosterone and other signaling pathways linked to sodium regulation will be determined. We will alter the expression of the miR-23~24~27 clusters to demonstrate its importance in maintaining sodium balance in the kidney. Finally the mechanism of intersectin-2 regulation of the epithelial sodium channel will be determined, to characterize the involvement of this novel aldosterone-repressed protein in Na+ regulation in the kidney.

 描述(由申请人提供)：这项建议将调查小的非编码RNA，称为microRNAs(MiRs)，在调节钠(Na+)在远端肾单位的运输中的作用。我们将探讨矿物皮质激素--醛固酮调节远端肾单位皮质集合管中特定miR簇的表达，从而通过靶向支架蛋白Intersectin-2的表达来改变Na+转运的假说。利用活体小鼠模型，我们将在CCD的主细胞中建立miRs的调节。由醛固酮和其他与钠调节相关的信号通路改变的显著调节的miRs将被确定。我们将改变miR-23~24~27簇的表达，以证明其在维持肾脏钠平衡中的重要性。最后，将确定交叉素-2调节上皮钠通道的机制，以表征这种新的醛固酮抑制蛋白参与肾脏钠离子调节的过程。