The FASEB journal, 2016-04, Vol.30 (4), p.1610-1622
2016
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- Autor(en) / Beteiligte
- Titel
- Activated mineralocorticoid receptor regulates micro‐RNA‐29b in vascular smooth muscle cells
- Ist Teil von
- The FASEB journal, 2016-04, Vol.30 (4), p.1610-1622
- Ort / Verlag
- Bethesda, MD, USA: Federation of American Societies for Experimental Biology
- Erscheinungsjahr
- 2016
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- 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 aldosterone via the MR reduces miR‐29b in vivo in 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. FASEB J. 30, 1610–1622 (2016). www.fasebj.org
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0892-6638eISSN: 1530-6860DOI: 10.1096/fj.15-271254Titel-ID: cdi_crossref_primary_10_1096_fj_15_271254
- Format
- –
- Schlagworte
- aldosterone, Aldosterone - pharmacology, Animals, Aorta - drug effects, Aorta - metabolism, Apoptosis - genetics, Cell Line, Cell Movement - drug effects, Cell Movement - genetics, Cell Proliferation - genetics, Cells, Cultured, Collagen - metabolism, Fibronectins - metabolism, Humans, Mice, Inbred C57BL, MicroRNAs - genetics, Muscle, Smooth, Vascular - cytology, Myocytes, Smooth Muscle - drug effects, Myocytes, Smooth Muscle - metabolism, Oligonucleotide Array Sequence Analysis, post‐transcriptional regulation, Receptors, Mineralocorticoid - agonists, Receptors, Mineralocorticoid - genetics, Reverse Transcriptase Polymerase Chain Reaction, Transcriptome - drug effects, Transcriptome - genetics, vascular aging, vascular disease