title: Activated mineralocorticoid receptor regulates micro-RNA-29b in vascular smooth muscle cells.
abstract: Inappropriately activated mineralocorticoid receptor (MR) is a risk factor for vascular remodeling with unclear molecular mechanism. Recent findings suggest that post-transcriptional regulation by micro-RNAs (miRs) may be involved. Our aim was to search for MR-dependent miRs in vascular smooth muscle cells (VSMCs) and to explore the underlying molecular mechanism and the pathologic relevance. We detected that aldosteroneviathe MR reduces miR-29bin vivoin murine aorta and in human primary and cultured VSMCs (ED50= 0.07 nM) but not in endothelial cells [quantitative PCR (qPCR), luciferase assays]. This effect was mediated by an increased decay of miR-29b in the cytoplasm with unchanged miR-29 family member or primary-miR levels. Decreased miR-29b led to an increase in extracellular matrix measured by ELISA and qPCR and enhanced VSMC migration in single cell-tracking experiments. Additionally, cell proliferation and the apoptosis/necrosis ratio (caspase/lactate dehydrogenase assay) was modulated by miR-29b. Enhanced VSMC migration by aldosterone required miR-29b regulation. Control experiments were performed with scrambled RNA and empty plasmids, by comparing aldosterone-stimulated with vehicle-incubated cells. Overall, our findings provide novel insights into the molecular mechanism of aldosterone-mediated vascular pathogenesis by identifying miR-29b as a pathophysiologic relevant target of activated MR in VSMCs and by highlighting the importance of miR processing for miR regulation.-Bretschneider, M., Busch, B., Mueller, D., Nolze, A., Schreier, B., Gekle, M., Grossmann, C. Activated mineralocorticoid receptor regulates micro-RNA-29b in vascular smooth muscle cells.
authors.affiliation: *Julius Bernstein Institute of Physiology and Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bretschneider
authors.affiliation: *Julius Bernstein Institute of Physiology and Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Busch
authors.affiliation: *Julius Bernstein Institute of Physiology and Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mueller
authors.affiliation: *Julius Bernstein Institute of Physiology and Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nolze
authors.affiliation: *Julius Bernstein Institute of Physiology and Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schreier
authors.affiliation: *Julius Bernstein Institute of Physiology and Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gekle
authors.affiliation: *Julius Bernstein Institute of Physiology and Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany claudia.grossmann@medizin.uni-halle.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Grossmann
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018161:Receptors, Mineralocorticoid / Q000819:agonists / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D005353:Fibronectins; C547014:MIRN29 microRNA, mouse; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003094:Collagen
keywords: aldosterone; post-transcriptional regulation; vascular aging; vascular disease