Abstract
Transforming growth factor-β (TGF-β) is closely associated with progressive renal fibrosis. A central component of TGF-β-stimulated mesangial cell fibrogenesis is the TGF-β family-specific Smad signal transduction pathway. This study investigated the expression of TGF-β-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-β1. However, amlodipine (10−7 to 10−5 mol/l) reduced the toxicity of rat mesangial cells induced by TGF-β1 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-β1; amlodipine (10−6, 10−5 mol/l) had no effect on Smad2 mRNA and protein expression induced by adriamycin + TGF-β1, 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-β1 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-β/Smad signaling intermediates p-Smad2 and Smad4.
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This work was supported by a research grant (No.30772680) from the National Natural Science Foundation of China.
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Song, YJ., Li, J., Xie, XF. et al. Effects of amlodipine on TGF-β-induced Smad2, 4 expressions in adriamycin toxicity of rat mesangial cells. Arch Toxicol 85, 663–668 (2011). https://doi.org/10.1007/s00204-011-0667-4
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DOI: https://doi.org/10.1007/s00204-011-0667-4