Effects of amlodipine on TGF-ß-induced Smad2, 4 expressions in adriamycin toxicity of rat mesangial cells.
Arch Toxicol
; 85(6): 663-8, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21337027
ABSTRACT
Transforming growth factor-ß (TGF-ß) is closely associated with progressive renal fibrosis. A central component of TGF-ß-stimulated mesangial cell fibrogenesis is the TGF-ß family-specific Smad signal transduction pathway. This study investigated the expression of TGF-ß-receptor--activated Smad2, its common partner Smad4, and the phosphorylated Smad2 (p-Smad2) in adriamycin-induced toxicity of cultured rat mesangial cells. This in vitro study showed that amlodipine (10(-9) to 10(-5) mol/l) had no effect on the toxicity of rat mesangial cells induced by adriamycin in the absence of TGF-ß1. However, amlodipine (10(-7) to 10(-5) mol/l) reduced the toxicity of rat mesangial cells induced by TGF-ß1 in the absence of adriamycin; moreover, amlodipine (10(-8) to 10(-5) mol/l) significantly reduced adriamycin-induced cytotoxicity when it was given in combination with TGF-ß1; amlodipine (10(-6), 10(-5) mol/l) had no effect on Smad2 mRNA and protein expression induced by adriamycin + TGF-ß1, but it (10(-6), 10(-5) mol/l) dramatically inhibited the down-regulation of p-Smad2 protein expression as well as Smad4 mRNA and protein expression induced by adriamycin + TGF-ß1 in rat mesangial cells. Present study shows that amlodipine exerts a significant inhibition on adriamycin-induced toxicity in rat mesangial cells by affecting the expression of TGF-ß/Smad signaling intermediates p-Smad2 and Smad4.
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Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
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Regulação da Expressão Gênica
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Fator de Crescimento Transformador beta
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Anlodipino
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Substâncias Protetoras
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Células Mesangiais
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Proteína Smad2
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article