Effect of efonidipine on TGF-β1-induced cardiac fibrosis through Smad2-dependent pathway in rat cardiac fibroblasts

• Lei Bai

  Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan

• Hitomi Hirofumi

  Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan

• Mori Tatsuhiko

  Department of Internal Medicine III, Osaka Medical College, Japan

• Nagai Yukiko

  Life Sciences Research Center, Faculty of Medicine, Kagawa University, Japan

• Deguchi Kazushi

  Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Japan

• Mori Hirohito

  Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Japan

• Masaki Tsutomu

  Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Japan

• Nakano Daisuke

  Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan

• Kobori Hiroyuki

  Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan

• Kitaura Yasushi

  Department of Internal Medicine III, Osaka Medical College, Japan

• Nishiyama Akira

  Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan

書誌事項

タイトル別名

• Effect of Efonidipine on TGF-.BETA.1-Induced Cardiac Fibrosis Through Smad2-Dependent Pathway in Rat Cardiac Fibroblasts
• Effect of efonidipine on TGF v 1 induced cardiac fibrosis through Smad2 dependent pathway in rat cardiac fibroblasts

抄録

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.

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 117 (2), 98-105, 2011

  公益社団法人 日本薬理学会

キーワード

• transforming growth factor beta-1
• Smad2
• T-type calcium channel
• cardiac fibrosis
• efonidipine

詳細情報

• CRID: 1390282680155106048
• NII論文ID: 10029896161
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.11065fp
• COI: 1:CAS:528:DC%2BC3MXhsVSrtbjK
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 11285987
• PubMed: 21897055
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I11285987
• Web Site: https://search.jamas.or.jp/link/ui/2012272369
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可