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）：本提案将研究小非编码 RNA（称为 microRNA (miR)）在调节远端肾单位钠 (Na+) 转运中的作用。我们将研究盐皮质激素的假设。 , 醛固酮调节远端肾单位皮质集合管 (CCD) 中特定 miR 簇的表达，通过靶向支架的表达来改变 Na+ 转运蛋白质 intersectin-2。我们将使用体内小鼠模型建立 CCD 主细胞中 miR 的调节，并确定受醛固酮和其他与钠调节相关的信号通路改变的显着调节的 miR。 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intersectin-2调节上皮钠通道的机制，以表征该新颖的参与。醛固酮抑制蛋白在肾脏中 Na+ 调节中的作用。