Chi Jinyu, Wang Lei, Zhang Xiaohui, Fu Yu, Liu Yue, Chen Wenjia, Liu Wenxiu, Shi Zhiyu, Yin Xinhua
Department of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin 150001, China.
Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37 YiYuan Street, Harbin 150001, China.
Biochem Biophys Res Commun. 2018 Mar 4;497(2):571-576. doi: 10.1016/j.bbrc.2018.02.098. Epub 2018 Feb 13.
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, 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.
心脏纤维化是心室重构的主要机制之一，且尚无有效的逆转方法。据报道，钙敏感受体（CaSR）的激活参与了心肌纤维化的发展，但CaSR激活的分子机制尚未阐明，有待进一步探索。在此，我们发现血管紧张素II（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，同时CaSR和自噬相关蛋白（Beclin1、LC3B）的表达增加。CaSR激活导致细胞内钙释放、MEK1/2通路磷酸化、自噬激活以及AngII诱导的心脏成纤维细胞中胶原蛋白形成。然而，用Calhex、PD98059或3-MA预处理细胞可部分阻断AngII诱导的心脏纤维化。我们的数据表明，CaSR介导的MEK/ERK和自噬通路的激活参与了体外AngII诱导的心脏纤维化。
