A microRNA cluster miR‐23/24/27 is regulated by aldosterone to alter Na + transport in the kidney distal nephron (711.5)

The epithelial sodium channel (ENaC) is a major determinant of sodium (Na+) and water balance in the kidney. We previously reported that aldosterone (aldo) modifies expression of microRNAs (miRs) to alter target gene expression and regulate Na+ transport in principal cortical collecting duct (CCD) epithelial cells. These studies focus on 2 clusters of miRs that are significantly upregulated by aldo, and are members of the miR‐23/24/27 family. In cultured mCCD‐cl1 cells, aldo stimulation (50nM, 24hr) resulted in a ~1.7 fold increase in all family members as determined by microarray and qPCR. In vivo, these miRs were significantly increased (1.7‐3.5 fold) in isolated CCD cells from mice on low Na+ vs standard salt diets. Exogenous overexpression on the miRs, using oligonucleotide mimics, increased ENaC‐mediated Na+ transport in the mCCD cell line (44±5.9%, n=8, p<0.002), in the absence of aldo stimulation. Using our newly developed algorithm, ComiR, we predicted and verified regulation of intersectin 1&2 as targets of these miR clusters, and possible mediators of ENaC regulation. These data confirm a central role for aldo‐regulated miRs in the maintenance of Na+ transport in the distal kidney nephron. Grant Funding Source : Supported by DK078917