Effect of Efonidipine on TGF-β1–Induced Cardiac Fibrosis Through Smad2-Dependent Pathway in Rat Cardiac Fibroblasts

Journal of Pharmacological Sciences

Akira Nishiyama¹  Hirofumi Hitomi¹  Bai Lei¹  Yasushi Kitaura⁴  Daisuke Nakano¹  Tsutomu Masaki²  Kazushi Deguchi²  Tatsuhiko Mori⁴  Hiroyuki Kobori¹  Yukiko Nagai³  Hirohito Mori² 

[1] Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan;Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Japan;Life Sciences Research Center, Faculty of Medicine, Kagawa University, Japan;Department of Internal Medicine III, Osaka Medical College, Japan

关键词: transforming growth factor beta-1;    Smad2;    T-type calcium channel;    cardiac fibrosis;    efonidipine;   

DOI  :  10.1254/jphs.11065FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(38)Cited-By(13)Transforming growth factor beta-1 (TGF-β1) plays a critical role in progression of cardiac fibrosis, which may involve intracellular calcium change. We examined effects of efonidipine, a dual T-type and L-type calcium channel blocker (CCB), on TGF-β1–induced fibrotic changes in neonatal rat cardiac fibroblast. T-type and L-type calcium channel mRNAs were highly expressed in cultured cardiac fibroblasts. TGF-β1 (5 ng/mL) significantly increased Smad2 phosphorylation and [3H]-leucine incorporation, which were attenuated by pretreatment with efonidipine (10 μM). Neither R(−)efonidipine (10 μM), selective T-type CCB, nor nifedipine (10 μM), selective L-type CCB, efficaciously inhibited both TGF-β1–induced Smad2 phosphorylation and [3H]-leucine incorporation. However, both were markedly attenuated by combination of R(−)efonidipine and nifedipine, EDTA, or calcium-free medium. Pretreatment with Smad2 siRNA significantly attenuated [3H]-leucine incorporation induced by TGF-β1. These data suggest that efonidipine elicits inhibitory effects on TGF-β1– and Smad2-dependent protein synthesis through both T-type and L-type calcium channel–blocking actions in cardiac fibroblasts.

【 授权许可】

Unknown