Role of MicroRNAs in Kidney Sodium Regulation

项目概要/摘要 这项提案将研究小的非编码RNA，称为microRNA（miRs），在调控中的作用。 钠（Na+）转运的远端肾脏肾单位。我们将调查的假设， 盐皮质激素醛固酮调节远端肾脏中特定miR簇的表达 肾单位皮质集合管（CCD）。这些miR靶向mRNA以改变Na+转运。膨胀- 调节醛固酮诱导的miRs，然后反馈减少醛固酮反应（阴性 反馈调节）。我们建议使用miR簇来测试miR在Na+稳态中的这种新作用， KO鼠标线。miR-17~92簇将使用条件性、可诱导的 KO线和长期醛固酮信号传导的影响将进行研究。第二部分 建议，醛固酮调节的miR用于改变Na+转运的机制将在 原代肾细胞

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.