title: A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport.
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.
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Edinger
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Klemens
authors.affiliation: Division of Nephrology in the Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Yu L
authors.initials: YL
authors.lastname: Phua
authors.affiliation: Division of Nephrology in the Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bodnar
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: William A
authors.initials: WA
authors.lastname: LaFramboise
authors.affiliation: Division of Nephrology in the Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ho
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Butterworth
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D020413:3' Untranslated Regions; D033942:Adaptor Proteins, Vesicular Transport; D053503:Epithelial Sodium Channels; C509777:Itsn2 protein, mouse; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; C529080:Mirn24 microRNA, mouse; C540674:Mirn27 microRNA, mouse; D012333:RNA, Messenger; D000450:Aldosterone; D012964:Sodium; D043244:Ribonuclease III