Role of MicroRNAs in Kidney Sodium Regulation

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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.