Role of MicroRNAs in Kidney Sodium Regulation

项目摘要/摘要 这项提案将调查被称为microRNAs(MiRs)的小非编码RNA在调控中的作用 钠(Na)在远端肾单位的转运。我们将调查一种假设，即 糖皮质激素--醛固酮调节远端肾脏特异性miR簇的表达 肾单位皮质集合管(CCD)。这些miRs以mRNAs为靶点改变钠的运输。花光了- 调节醛固酮诱导的MIR，然后反馈以减少醛固酮反应(阴性 反馈调节)。我们建议测试miRs在钠稳态中的这一新作用，但使用miR簇 KO鼠系。MiR-17~92簇将使用有条件的、可诱导的从肾单位中删除 并对其对长期醛固酮信号转导的影响进行研究。在第二部分中， 提案中，将研究醛固酮调节的MIR用来改变钠转运的机制 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.