Effect of Efonidipine on TGF-β1–Induced Cardiac Fibrosis Through Smad2-Dependent Pathway in Rat Cardiac Fibroblasts
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概要
- 論文の詳細を見る
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.
著者
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Mori Tatsuhiko
Department Of Internal Medicine Iii Osaka Medical College
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Nagai Yukiko
Life Science Research Center Kagawa University Medical School
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Masaki Tsutomu
Department Of Cell Physiology Faculty Of Medicine Kagawa University
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Nakano Daisuke
Department Of Organic Chemistry Graduate School Of Pharmaceutical Sciences Tohoku University
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Nishiyama Akira
Department Of Pharmacology Faculty Of Medicine Kagawa University
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Takaoka M
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Kobori Hiroyuki
Department Of Obstetrics And Gynaecology Juntendo University School Of Medicine
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Kitaura Yasushi
Department Of Cardiology Institute Of Clinical Medicine University Of Tsukuba
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Lei Bai
Department Of Pharmacology Faculty Of Medicine Kagawa University
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Hitomi Hirofumi
Department Of Pharmacology Faculty Of Medicine Kagawa University
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Mori Hirohito
Department Of Gastroenterology And Neurology Faculty Of Medicine Kagawa University
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Deguchi Kazushi
Department Of Gastroenterology And Neurology Faculty Of Medicine Kagawa University
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