title: Effects of amlodipine on TGF-β-induced Smad2, 4 expressions in adriamycin toxicity of rat mesangial cells.
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.
authors.affiliation: Department of Pharmacology, Research Center of Food and Drug evaluation, Basic Medical School, Wuhan University, 430071, Wuhan, China.
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Song
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Xian-Fei
authors.initials: XF
authors.lastname: Xie
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Qi-Xiong
authors.initials: QX
authors.lastname: Li
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000959:Antihypertensive Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000633:toxicity
chemical_list: D000903:Antibiotics, Antineoplastic; D000959:Antihypertensive Agents; D020011:Protective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017311:Amlodipine; D004317:Doxorubicin