Aldosterone induces CTGF in mesangial cells by activation of the glucocorticoid receptor.
BACKGROUND
Aldosterone contributes substantially to cardiac and renal injury by acting on target cells not involved in the regulation of salt and water balance. The profibrotic protein connective tissue growth factor (CTGF) has been identified as one of the target proteins of aldosterone. However, the molecular mechanisms of aldosterone-mediated CTGF induction have not been characterized.


METHODS
Mesangial cells were treated with aldosterone or dexamethasone. CTGF expression was characterized at the mRNA and protein level. Translocation of the glucocorticoid receptor (GR) was detected by immunocytochemistry and by Western blotting.


RESULTS
Aldosterone and dexamethasone induced CTGF at the mRNA and protein level in a time- and concentration-dependent manner. Specific antagonists of the mineralocorticoid receptor, spironolactone, canrenoate or eplerenone, did not inhibit CTGF induction. However, inhibition of the GR by RU486 prevented dexamethasone-as well as aldosterone-induced CTGF expression, indicating the importance of the GR in aldosterone-mediated regulation of CTGF. This notion was confirmed by translocation of the GR to the nucleus upon stimulation with aldosterone.


CONCLUSIONS
CTGF is a functional target of aldosterone in mesangial cells, but aldosterone-induced CTGF gene expression is not directly mediated by the mineralocorticoid receptor.
Gauer
Stefan
S
Department of Nephrology and Hypertension, Medical Clinic 4, University of Erlangen-Nuremberg, Loschgestrasse 8, D-91054 Erlangen, Germany.
Segitz
Verena
V
Goppelt-Struebe
Margarete
M
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques; D055513:Connective Tissue Growth Factor; D003907:Dexamethasone / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007700:Kinetics; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D055513:Connective Tissue Growth Factor; D013148:Spironolactone; D000450:Aldosterone; D003907:Dexamethasone