Aldosterone Upregulates Connective Tissue Growth Factor Gene Expression via p38 MAPK Pathway and Mineralocorticoid Receptor in Ventricular Myocytes
Journal of Korean Medical Science
;
: 805-811, 2004.
Artigo
em Inglês
| WPRIM
| ID: wpr-27632
ABSTRACT
The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pat-tern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each path-way revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Espironolactona
/
Transdução de Sinais
/
Regulação para Cima
/
Células Cultivadas
/
Regulação da Expressão Gênica
/
Receptores de Mineralocorticoides
/
Proteínas Imediatamente Precoces
/
Miócitos Cardíacos
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Proteínas Quinases p38 Ativadas por Mitógeno
Limite:
Animais
Idioma:
Inglês
Revista:
Journal of Korean Medical Science
Ano de publicação:
2004
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS