Aldosterone-induced TGF-beta1 expression is regulated by mitogen-activated protein kinases and activator protein-1 in mesangial cells.
Aldosterone has been shown to stimulate renal TGF-beta(1) expression. However, the mechanisms for aldosterone-induced TGF-beta(1) 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-beta(1) expression in rat mesangial cells. TGF-beta(1) protein in the conditioned medium released from rat mesangial cells was measured by sandwich ELISA, TGF-beta(1) 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-beta(1) protein production and TGF-beta(1) 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-beta(1) 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-beta(1) production, respectively. We conclude that aldosterone-induced TGF-beta(1) expression in mesangial cells is regulated by the ERK1/2, JNK and AP-1 intracellular signaling pathways.
Han
Jeong-Sun
JS
Renal Research Laboratory, Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea.
Choi
Bum-Soon
BS
Yang
Chul-Woo
CW
Kim
Yong-Soo
YS
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020935:MAP Kinase Signaling System; D050527:Mesangial Cells / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
D017077:Culture Media, Conditioned; D018808:Transcription Factor AP-1; D053773:Transforming Growth Factor beta1; D000450:Aldosterone; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases