Non-classical actions of the mineralocorticoid receptor: misuse of EGF receptors?
The mineralocorticoid receptor (MR) plays a key role in cardiovascular and renal injury. The underlying mechanisms seem to involve the epidermal growth factor receptor (EGFR) for the development of fibrosis and vascular dysfunction. Both enhanced EGFR transactivation by activated MR as well as upregulation of EGFR expression by aldosterone-bound MR have been described. While the former seems to be mediated by the tyrosine kinase cSrc, reporter gene assays and chromatin immunoprecipitation data indicate that the latter is caused by an interaction between MR and the EGFR promoter. Pharmacological inhibition of EGFR function prevents some of MR's pathological actions in cell culture systems, like vascular smooth muscle cells. Thus, transactivation as well as enhanced expression of EGFR may be an important switch for the pathophysiological actions in the reno-cardiovascular continuum. Furthermore, EGFR signaling may serve as a negative feedback loop to limit sodium retention. Overall, MR's "misuse" of the EGFR is one possible explanation for the pathophysiological effects of aldosterone, making the EGFR a potential target for therapeutical interventions against reno-cardiovascular remodelling.
Grossmann
Claudia
C
Julius-Bernstein-Institut für Physiologie, Universität Halle-Wittenberg, Magdeburger Strasse 6, 06097 Halle, Saale, Germany.
Gekle
Michael
M
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D066246:ErbB Receptors; D016392:Proto-Oncogene Proteins pp60(c-src); D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3