Activation of calcium-sensing receptor-mediated autophagy in angiotensinII-induced cardiac fibrosis in vitro
Activation of calcium-sensing receptor-mediated autophagy in angiotensinII-induced cardiac fibrosis in vitro
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DOI：
10.1016/j.bbrc.2018.02.098
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发表时间：
2018-03-04
影响因子：
3.1
通讯作者：
Yin, Xinhua
中科院分区：
文献类型：
--
作者：
Chi, Jinyu;Wang, Lei;Yin, Xinhua
心肌纤维化是心室重构的主要机制之一，目前尚无有效的逆转方法。钙敏感受体（calcium sensing receptor, CaSR）的激活已被报道参与心肌纤维化的发生发展，但CaSR激活的分子机制尚未明确，需要进一步探索。在这里，我们发现AngII以剂量依赖的方式诱导心脏成纤维细胞增殖和表型转化，增加CaSR和自噬相关蛋白（Beclin1, LC3B）的表达。CaSR激活导致心肌成纤维细胞细胞内钙释放、MEK1/2通路磷酸化、自噬激活和AngII诱导的胶原形成。然而，用Calhex（231）、PD98059或3-MA预处理细胞可部分阻断血管i诱导的心脏纤维化。我们的数据表明，casr介导的MEK/ERK和自噬途径的激活参与了体外血管诱导的心脏纤维化。(C) 2018爱思唯尔公司版权所有。
Cardiac fibrosis is one of the primary mechanisms of ventricular remodeling, and there is no effective method for reversal. Activation of calcium sensing receptor (CaSR) has been reported to be involved in the development of myocardial fibrosis, but the molecular mechanism for CaSR activation has not yet been clarified and needs to be further explored. Here, we found that AngII induces cardiac fibroblast proliferation and phenotypic transformation in a dose-dependent manner with increased CaSR and autophagy related protein (Beclin1, LC3B) expression. CaSR activation results in intracellular calcium release, MEK1/2 pathway phosphorylation, autophagy activation and collagen formation induced by AngII in cardiac fibroblasts. However, pretreating the cells with Calhex(231), PD98059 or 3-MA partially blocked AngII-induced cardiac fibrosis. Our data indicate that the activation of CaSR-mediated MEK/ERK and autophagic pathways is involved in AngII-induced cardiac fibrosis in vitro. (C) 2018 Elsevier Inc. All rights reserved.