Eplerenone Prevents Atrial Fibrosis via the TGF-β Signaling Pathway
Eplerenone Prevents Atrial Fibrosis via the TGF-β Signaling Pathway
复制标题
依普利农通过 TGF-β 信号通路预防心房纤维化
DOI：
10.1159/000471918
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发表时间：
2017-08-01
期刊：
影响因子：
1.9
通讯作者：
Duan, Sheng-Zhong
中科院分区：
文献类型：
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作者：
Du, Lili;Qin, Mu;Duan, Sheng-Zhong
目的：依普利酮 (EPL) 是一种盐皮质激素受体拮抗剂，有益于治疗心房颤动和心房纤维化。然而，其基本机制仍然不太为人所知。我们的目的是使用选择性心房纤维化小鼠研究 EPL 对心房纤维化的影响，并探讨其潜在机制。方法：使用 EPL 治疗的具有选择性心房纤维化的 MHC-TGFcys 33 ser 转基因小鼠（Tx+ EPL 小鼠）以及对照小鼠进行体内研究，包括组织学分析、蛋白质印迹和 qRT-PCR 研究。用 EPL 或载体处理 TGF-β(1) 刺激的心房成纤维细胞，进行体外研究，包括蛋白质印迹和 qRT-PCR 研究。此外，使用Smad7 siRNA来敲低Smad7。结果：EPL 抑制 Tx 小鼠的心房纤维化。此外，EPL在体内和体外抑制TGF-β(1)诱导的纤维化相关分子的表达。这与 Smad7 蛋白表达的下调和 p-Smad2/3 蛋白表达的上调同时发生。此外，通过 siRNA 敲低 Smad7 消除了 EPL 的保护作用。结论：EPL 抑制 Tx 小鼠的心房纤维化。潜在机制可能涉及 Smad7 蛋白表达增加，从而增强 TGF-β(1)/Smad 信号传导的抑制性反馈调节。 (C) 2017 S. Karger AG，巴塞尔
Objectives: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. Methods: EPL-treated MHC-TGFcys 33 ser transgenic mice that have selective atrial fibrosis (Tx+ EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies. TGF-beta(1) -stimulated atrial fibroblasts were treated with EPL or vehicle for the in vitro studies including Western blotting and qRT-PCR studies. In addition, Smad7 siRNA was used to knock down Smad7. Results: EPL inhibited atrial fibrosis in the Tx mice. In addition, EPL suppressed the expression of fibrosis-related molecules induced by TGF-beta(1) in vivo and in vitro. This occurred in concert with a downregulation of Smad7 protein expression and an upregulation of p-Smad2/3 protein expression. In addi-tion, knockdown of Smad7 by siRNA abolished the protective roles of EPL. Conclusions: EPL inhibited atrial fibrosis in Tx mice. The underlying mechanism may involve increased protein expression of Smad7, which enhances the inhibitory feedback regulation of TGF- beta(1)/Smad signaling. (C) 2017 S. Karger AG, Basel