Aldosterone-induced TGF-beta1 Expression is Regulated by Mitogen-Activated Protein Kinases and Activator Protein-1 in Mesangial Cells.
10.3346/jkms.2009.24.S1.S195
- Author:
Jeong Sun HAN
1
;
Bum Soon CHO
;
Chul Woo YANG
;
Yong Soo KIM
Author Information
1. Renal Research Laboratory, Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Aldosterone;
Transforming Growth Factor beta1;
Extracellular Signal-Regulated MAP Kinases;
JNK Mitogen-Activated Protein Kinases;
Transcription Factor AP-1
- MeSH:
Aldosterone/*pharmacology;
Animals;
Culture Media, Conditioned/pharmacology;
DNA/metabolism;
Extracellular Signal-Regulated MAP Kinases/metabolism;
*Gene Expression Regulation, Enzymologic;
Humans;
*MAP Kinase Signaling System;
Mesangial Cells/*metabolism;
Models, Biological;
Phosphorylation;
Protein Binding;
Rats;
Transcription Factor AP-1/*metabolism;
Transforming Growth Factor beta1/*biosynthesis
- From:Journal of Korean Medical Science
2009;24(Suppl 1):S195-S203
- CountryRepublic of Korea
- Language:English
-
Abstract:
Aldosterone has been shown to stimulate renal TGF-beta1 expression. However, the mechanisms for aldosterone-induced TGF-beta1 expression have not been clearly determined in mesangial cells. We examined the role of extracellular-signal regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and activator protein- 1 (AP-1) in the aldosterone-induced TGF-beta1 expression in rat mesangial cells. TGF-beta1 protein in the conditioned medium released from rat mesangial cells was measured by sandwich ELISA, TGF-beta1 mRNA expression was analyzed by Northern blotting, AP-1 DNA binding activity was measured by EMSA and the ERK1/2, JNK activity was analyzed by western blotting. Aldosterone significantly stimulated TGF-beta1 protein production and TGF-beta1 mRNA expression in mesangial cells in a dose-dependent manner. Aldosterone significantly increased AP-1 DNA binding activity in mesangial cells. Pre-treatment of cells with AP-1 inhibitor, curcumin, blocked aldosterone-induced AP-1 DNA binding activity as well as aldosterone-induced TGF-beta1 production. Aldosterone increased phosphorylation of ERK1/2 and JNK in mesangial cells. Pre-treatment of cells with ERK1/2 inhibitor, PD98059, or JNK inhibitor, SP600125 significantly inhibited aldosterone-induced ERK1/2 and JNK activity and subsequently TGF-beta1 production, respectively. We conclude that aldosteroneinduced TGF-beta1 expression in mesangial cells is regulated by the ERK1/ 2, JNK and AP-1 intracellular signaling pathways.
