The role of miRNAs in mineralocorticoid receptor modulated gene expression
Prof. Gekle, JProf. Großmann
Steroid hormone receptors are ligand-dependent transcription factors that control a variety of homeostatic functions, starting from salt metabolism to sexual behavior. It is now evident that steroid hormone receptors do not follow a simple on/off switch model, but depend on the interaction with different signaling networks 1. Although for some steroid hormone receptors information is available 2, for the mineralocorticoid receptor (MR) very little is known. The MR controls extracellular volume, long-term regulation of blood pressure and homeostatic behavior. MR also promotes renocardiovascular inflammation and fibrosis independently of blood pressure and salt homeostasis 3. As a ligand-dependent transcription factor 4, MR modulates the expression of proteins. Furthermore, MR interacts non-genomically with cytosolic signaling pathways, including calcium and protein kinases in different cell types 5-7. Its closest relative, the glucocorticoid receptor (GR), is important for e.g. development, glucose/lipid metabolism and immune function. Although the cellular and systemic effects of MR-activation are clearly distinct from GR-activation, the mechanism of their differential action is not understood. So far no mineralocorticoid-response element has been identified in promoters and most genes induced by MR are also induced by GR. Control of miRNA expression by MR would offer an additional level of regulation which has not been investigated until today. This function could contribute to differential effects compared with its closest relative glucocorticoid receptors. In recent years the importance of altered miRNA expression for the renocardiovascular system has been shown and gains rapid growing consideration. Thus, our project is of basic and clinical relevance.
Mineralocorticoid receptor, Transcription factor
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