Non-coding RNAs and the mineralocorticoid receptor in the kidney

Abstract

The final steps in the Renin-Angiotensin-Aldosterone signaling System (RAAS) involve binding of the corticosteroid hormone, aldosterone to its mineralocorticoid receptor (MR). The bound MR interacts with response elements to induce or repress the transcription of aldosterone-regulated genes. Along with the classic genomic targets of aldosterone that alter mRNA and protein expression, aldosterone also regulates the expression of non-coding RNAs (ncRNAs). Short ncRNAs termed microRNAs (miRs) have been shown to play a role in transducing aldosterone's actions via MR signaling. The role of miRs in homeostatic regulation of aldosterone signaling, and the potential for aldosterone-regulated miRs to act as feedback regulators of MR have been recently reported. In this review, the role of miRs in RAAS signaling and feedback regulation of MR in kidney epithelial cells will be discussed.

Keywords: Aldosterone; MR; Mineralocorticoid receptor; Non-coding RNA; RAAS; miR; microRNA; ncRNA.

Figure 1:

A schematic figure outlining the miR signaling pathways established by aldosterone stimulation through the MR. Red lines represent repression and green arrows stimulation of expression. It is likely that several of the miRs induced by aldosterone, feedback to negatively regulate parts of the RAAS signaling pathway (long feedback loop). There is evidence for localized feedback with miR-466 repressing the expression of MR and SGK1 in the same cells that are stimulated by aldosterone (short feedback loop). The miRs and targets depicted in this figure are discussed in the text.