Identification of Mineralocorticoid-responsive Elements (MRE)

• Applicant: Professorin Dr. Claudia Grossmann
• Subject Area: Anatomy and Physiology
• Term: from 2004 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5422002

The mineralocorticoid receptor (MR) plays an important role in water electrolyte homeostasis and additionally mediates pathological effects in the renocardiovascular system, including inflammation, endothelial dysfunction, fibrosis and hypertrophy. In clinical studies, MR antagonists significantly improve pathological effects of MR in the renocardiovascular system and increase patient survival, thus proving their pathophysiological relevance. Nevertheless, the underlying molecular mechanisms remain elusive. Although MR and its closest relative, the glucocorticoid receptor (GR), share a common hormone responsive-element, the GR does not lead to pathological alterations in the renocardiovascular system but evokes anti-inflammatory and protective effects. Consequently, we propose the existence of additional, so far unknown MR-specific DNA-response-elements. In our previous work we identified an MR-specific, SP1-dependent DNA element located on the epidermal growth factor receptor (EGFR) promoter. Based on this finding, we aim to characterize the molecular mechanism of the interaction between MR, SP1 and MRE in more detail and explore its pathophysiological relevance. Subsequently, we will search for further MR-regulated genes that require SP1 and thereby test if the previously analyzed mechanism can be transferred to other genes. Overall, we intend to gain insights into the molecular mechanism of pathophysiological MR effects and signaling, which is of special relevance for developing therapeutic strategies or methods for prevention of MR-mediated diseases.

• DFG Programme: Research Grants