Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.
Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.
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DOI：
10.1371/journal.pone.0186635
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Pan L;Sheng M;Huang Z;Zhu Z;Xu C;Teng L;He L;Gu C;Yi C;Li J
本研究旨在探讨锌指蛋白418（ZNF 418）对主动脉缩窄（AB）、苯肾上腺素（PE）和血管紧张素II（Ang II）所致心肌肥厚的影响及其机制。采用Western blotting方法检测ZNF 418在扩张型心肌病（DCM）、肥厚型心肌病（HCM）患者和AB诱导的心肌肥厚小鼠心脏以及Ang II或PE诱导的肥大原代心肌细胞中的表达。ZNF 418的表达在AB诱导的心肌肥大小鼠和Ang II诱导的肥大原代心肌细胞中上调或下调。通过超声心动图和组织学分析评估肥大反应和纤维化。采用RT-qPCR方法检测心肌细胞肥大标志物和纤维化标志物的mRNA水平。此外，通过蛋白质印迹法测量c-Jun的磷酸化和总水平。ZNF 418在心肌肥大和肥大的原代心肌细胞中表达明显下调。ZNF 418基因敲除小鼠心肌组织中ANP、BNP、β-MHC、MCIP1.4、胶原1a、胶原III、MMP-2和纤维连接蛋白mRNA表达水平明显升高，AdshZNF 418基因敲除小鼠心肌组织中ANP、BNP、β-MHC、MCIP1.4、胶原1a、胶原III、MMP-2和纤维连接蛋白mRNA表达水平明显升高。相反，这些肥大反应在AB处理的ZNF 418转基因（TG）小鼠和Ang II处理的AdZNF 418转染的原代心肌细胞中减少。此外，ZNF 418的缺失增强了c-jun的磷酸化水平，ZNF 418的过表达抑制了c-jun的磷酸化水平。ZNF 418可能通过抑制c-jun/AP-1的活性而减轻肥大反应。
This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418) on cardiac hypertrophy caused by aortic banding (AB), phenylephrine (PE) or angiotensin II (Ang II) in vivo and in vitro. The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting. ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG) mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro. ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.
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DOI：
10.1186/1755-1536-5-15
发表时间：
2012-09-03
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Fan D;Takawale A;Lee J;Kassiri Z
通讯作者：
Kassiri Z
影响因子：
37.8
作者：
Kehat I;Molkentin JD
通讯作者：
Molkentin JD
影响因子：
3.7
作者：
Nowick K;Fields C;Gernat T;Caetano-Anolles D;Kholina N;Stubbs L
通讯作者：
Stubbs L
影响因子：
168.9
作者：
Maron, Barry J.;Maron, Martin S.
通讯作者：
Maron, Martin S.
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M