Effect of Efonidipine on TGF-β1–Induced Cardiac Fibrosis Through Smad2-Dependent Pathway in Rat Cardiac Fibroblasts
| Autor: | Akira Nishiyama, Hirohito Mori, Kazushi Deguchi, Tatsuhiko Mori, Bai Lei, Yasushi Kitaura, Daisuke Nakano, Yukiko Nagai, Hirofumi Hitomi, Hiroyuki Kobori, Tsutomu Masaki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Dihydropyridines
medicine.medical_specialty Calcium Channels L-Type Nifedipine medicine.drug_class Cardiac fibrosis chemistry.chemical_element Efonidipine Smad2 Protein Calcium channel blocker Calcium Transfection Article Calcium in biology Nitrophenols Rats Sprague-Dawley Transforming Growth Factor beta1 Calcium Channels T-Type Organophosphorus Compounds Internal medicine medicine Animals RNA Small Interfering Pharmacology business.industry Myocardium Calcium channel lcsh:RM1-950 T-type calcium channel Fibroblasts Calcium Channel Blockers medicine.disease Fibrosis Rats Endocrinology lcsh:Therapeutics. Pharmacology chemistry Molecular Medicine business medicine.drug |
| Zdroj: | Journal of Pharmacological Sciences, Vol 117, Iss 2, Pp 98-105 (2011) |
| ISSN: | 1347-8613 |
| Popis: | 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. Keywords:: transforming growth factor beta-1, Smad2, T-type calcium channel, cardiac fibrosis, efonidipine |
| Databáze: | OpenAIRE |
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