title: Amlodipine prevents adriamycin-induced toxicity in cultured rat mesangial cells by up-regulation of Smad6, Smad7 expression.
abstract: Extensive studies have demonstrated that transforming growth factor-beta (TGF-β) plays an important role in the progression of renal diseases. A central component of TGF-β is the TGF-β family-specific Smad signal transduction pathway. TGF-β signals through Smad2, 4 to mediate renal fibrosis, whereas induction of Smad6, 7 inhibits renal fibrosis and inflammation. Amlodipine is the most frequently used antihypertensive drug among dihydropyridines. It is beneficial to the kidney and is widely used in treating kidney diseases. The aim of this study was to investigate effects of amlodipine on adriamycin-induced changes of lactate dehydrogenase (LDH) and expression of Smad6, 7 in rat mesangial cells. Results showed that amlodipine (10(-8) to 10(-5)mol/l) significantly decreased LDH activity in rat mesangial cells when given in combination with TGF-β₁ (P<0.01); amlodipine (10(-7), 10(-6)mol/l) significantly increased Smad6, 7 mRNA and protein expression in cells treated with adriamycin and TGF-β₁ (P<0.01). In conclusion, amlodipine protects against adriamycin-induced toxicity in rat mesangial cells by up-regulation of Smad6, 7 expressions.
authors: Department of Laboratory, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, 430071 Wuhan, China.
authors: Jin
authors: J
authors: Li
authors: Department of Stomatology, Zhongnan Hospital of Wuhan University, 430071 Wuhan, China. Electronic address: ewysls@163.com.
authors: Chao-rong
authors: CR
authors: Tie
authors: Department of Pharmacology, Basic Medical School of Wuhan University, 430071 Wuhan, China.
authors: Qi-xiong
authors: QX
authors: Li
authors: Department of Laboratory, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, 430071 Wuhan, China. Electronic address: zhengfang@whu.edu.com.
authors: Fang
authors: F
authors: Zheng
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*; D050527:Mesangial Cells / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D051905:Smad6 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; D000959:Antihypertensive Agents; D051905:Smad6 Protein; C497804:Smad6 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta; D017311:Amlodipine; D004317:Doxorubicin
keywords: Adriamycin; Amlodipine; Mesangial cell; Smad6; Smad7