Question:

Steroid hormone receptors are ligand-dependent transcription factors that control a variety of homeostatic functions. The mineralocorticoid receptor (MR) as part of this family is involved in salt and water homeostasis but can also elicit pathophysiological effects in the renocardiovascular system leading to fibrosis and tissue remodeling. However, the molecular mechanisms underlying especially the pathophysiological MR effects are not yet understood. We wanted to investigate whether posttranscriptional regulation of genes by MR-dependent microRNAs is involved in mediating these MR effects.

Methods + Results:

To test the influence of activated MR on microRNA expression profiles in vascular cells, we stimulated primary human aortic vascular smooth muscle cells (HAoSMC) with the endogenous MR ligand aldosterone and screened for MR-regulated microRNAs by microarray analysis and deep sequencing. Candidates were then validated by Taqman qPCR and reporter gene assays. Our analysis highlighted miR-29b to be significantly regulated by aldosterone. The impact of changes in miR-29b expression on cell death was investigated through lactat dehydrogenase release assay (necrosis) and caspase activity analysis (apoptosis). In addition qPCR and ELISA assays were performed to detect the effect of miR-29b on extra cellular matrix components. MiR-29b was able to influence both extracellular matrix component composition and cell death in vascular smooth muscle cells.

Conclusions:

Overall, our data demonstrate that activated MR can regulate the expression of microRNAs including miR-29b in vascular smooth muscle cells. Because miR-29b can influence extracellular matrix composition and cell death, an involvement in mediating pathophysiological MR effects in the vasculature is an attractive hypothesis.