A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal
Kidney Nephron Where it Alters Sodium Transport.
Authors Liu X, Edinger RS, Klemens CA, Phua YL, Bodnar AJ, LaFramboise WA, Ho J,
Butterworth MB
Submitted By Submitted Externally on 5/17/2017
Status Published
Journal Journal of cellular physiology
Year 2017
Date Published 6/1/2017
Volume : Pages 232 : 1306 - 1317
PubMed Reference 27636893
Abstract The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the
distal convoluted tubules, connecting tubules, and cortical collecting duct
(CCD) in the kidney nephron. Under the regulation of the steroid hormone
aldosterone, ENaC is a major determinant of sodium (Na(+) ) and water balance.
The ability of aldosterone to regulate microRNAs (miRs) in the kidney has
recently been realized, but the role of miRs in Na(+) regulation has not been
well established. Here we demonstrate that expression of a miR cluster
mmu-miR-23-24-27, is upregulated in the CCD by aldosterone stimulation both in
vitro and in vivo. Increasing the expression of these miRs increased Na(+)
transport in the absence of aldosterone stimulation. Potential miR targets were
evaluated and miR-27a/b was verified to bind to the 3'-untranslated region of
intersectin-2, a multi-domain protein expressed in the distal kidney nephron and
involved in the regulation of membrane trafficking. Expression of Itsn2 mRNA and
protein was decreased after aldosterone stimulation. Depletion of Itsn2
expression, mimicking aldosterone regulation, increased ENaC-mediated Na(+)
transport, while Itsn2 overexpression reduced ENaC's function. These findings
reinforce a role for miRs in aldosterone regulation of Na(+) transport, and
implicate miR-27 in aldosterone's action via a novel target. J. Cell. Physiol.
232: 1306-1317, 2017. © 2016 Wiley Periodicals, Inc.