NDT Advance Access originally published online on June 30, 2007
Nephrology Dialysis Transplantation 2007 22(11):3154-3159; doi:10.1093/ndt/gfm410
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Aldosterone induces CTGF in mesangial cells by activation of the glucocorticoid receptor
1Department of Nephrology and Hypertension, Medical Clinic 4, University of Erlangen-Nuremberg, Germany and 2Department of Nephrology, Medical Clinic III, University of Frankfurt/Main, Germany
Correspondence and offprint requests to: Margarete Goppelt-Struebe, PhD, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Loschgestrasse 8, D-91054 Erlangen, Germany. Email: goppelt-struebe{at}rzmail.uni-erlangen.de
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Abstract |
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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.
Keywords: Aldosterone; connective tissue growth factor; dexamethasone; glucocorticoid receptor; mesangial cells; mineralocorticoid receptor
Received for publication: 14. 3.07
Accepted in revised form: 31. 5.07
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