title: Aldosterone stimulates epidermal growth factor receptor expression.
abstract: The steroid hormone aldosterone plays an important role during pathological tissue modifications, similar to cardiovascular or renal fibrosis. The underlying mechanisms for the pathological actions are not understood. Interaction of aldosterone with the epidermal growth factor (EGF) receptor is an attractive hypothesis to explain pathological tissue remodeling elicited by aldosterone, because (i) mineralocorticoids can sensitize cells for EGF, (ii) mineralocorticoid receptor (MR)-antagonists reduce EGFR-mRNA expression, (iii) EGFR itself supports the development of cardiovascular or renal fibrosis, and (iv) signaling elements involved in the pathological action of aldosterone (similar to ERK1/2 or NFkB) are typical downstream modules during EGF signaling. In addition, an interaction of aldosterone and EGF with respect to ERK1/2 activation has been described. Here we show that aldosterone stimulates EGFR expression in renal tissue of adrenalectomized rats and in human renal primary cell cultures. Furthermore, Chinese hamster ovary (CHO) cells normally devoid of EGFR or MR express EGFR after transfection with human MR (CHO-MR cells) but not after transfection with human glucocorticoid receptor (CHO-GR cells). In CHO-MR cells, EGFR-expression is up-regulated by aldosterone and inhibited by spironolactone. CHO-MR cells but not CHO-GR cells respond with ERK1/2 phosphorylation to EGF exposure. The responsiveness to other peptide hormones was virtually not affected. These data suggest that EGFR is an aldosterone-induced protein and is involved in the manifold (patho)biological actions of aldosterone.
authors.affiliation: Physiologisches Institut der Universität Würzburg, Würzburg 97070, Germany.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Krug
authors.forename: Claudia
authors.initials: C
authors.lastname: Grossmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Schuster
authors.forename: Ruth
authors.initials: R
authors.lastname: Freudinger
authors.forename: Sigrid
authors.initials: S
authors.lastname: Mildenberger
authors.forename: Manjapra V
authors.initials: MV
authors.lastname: Govindan
authors.forename: Michael
authors.initials: M
authors.lastname: Gekle
mesh_terms: D000450:Aldosterone / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D016466:CHO Cells; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000096:biosynthesis*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008901:Mineralocorticoids / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases