DACT2 regulates structural and electrical atrial remodeling in atrial fibrillation
DACT2 regulates structural and electrical atrial remodeling in atrial fibrillation
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DACT2 调节心房颤动中的结构和电心房重塑。
DOI：
10.21037/jtd-19-4206
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发表时间：
2020-05
影响因子：
2.5
通讯作者：
Wu Zhongkai
中科院分区：
文献类型：
--
作者：
Hou Jian;Huang Shaojie;Long Yan;Huang Jiaxing;Yang Song;Yao Jianping;Chen Guangxian;Yue Yuan;Liang Mengya;Mei Bo;Li Jiawen;Wu Zhongkai
背景：房颤是最常见的持续性心律失常。DACT2是一种新的重要的信号通路介体。本研究旨在探讨DACT2在房颤中的表达及其临床意义。方法：应用免疫组织化学方法检测DACT2在瓣膜病患者中的表达模式。DACT2在HL-1细胞和原代培养的心房成纤维细胞中高表达。用实时定量聚合酶链式反应检测钾通道、L型钙电流通道、钠离子通道蛋白和胶原蛋白的表达水平。Western blotting检测DACT2过表达后Wnt和转化生长因子-β信号转导通路中涉及的蛋白。结果：DACT2的表达与房颤的发生密切相关(P=0.016)。DACT2强表达组肝纤维化程度显著低于弱表达组(弱：0.198+/-0.091，强：0.129+/-0.064，P=0.048)，且DACT2表达水平与肝纤维化程度呈负相关(Spearman Rho=-0.476，P=0.010)。DACT2可显著上调KCNE5的表达水平，降低KCNH2和SCN5A的表达水平。DACT2过表达显著抑制原代培养的大鼠心房成纤维细胞I型和III型胶原的表达。DACT2可通过降低IL-1细胞Thr41/Ser45的磷酸化水平促进β-catenin的蓄积，并抑制原代培养的心房成纤维细胞中的转化生长因子-β信号通路。结论：DACT2通过调节心房结构重构和电重构、影响β-连环蛋白积聚和转化生长因子-β信号转导途径在房颤中发挥作用，对瓣膜病房颤有保护作用。
Background: Atrial fibrillation (AF) is the most common sustained arrhythmia. DACT2 is a novel and important mediator of signaling pathways. The aim of this study was to investigate the clinical significance and functions of DACT2 expression in AF. Methods: Immunohistochemistry was used to detect the DACT2 expression pattern in valvular disease patients. DACT2 was overexpressed in HL-1 cells and primary atrial fibroblasts. The expression levels of the potassium channel, the L-type calcium current channel, sodium ion channel proteins and collagen proteins were detected by real-time polymerase chain reaction (RT-PCR). The proteins involved in the Wnt and TGF-beta signaling pathways were detected after DACT2 overexpression by western blotting. Results: DACT2 expression was significantly associated with AF (P=0.016). The fibrosis ratio in the strong DACT2 expression group was significantly lower than that in the weak DACT2 expression group (weak: 0.198 +/- 0.091, strong: 0.129 +/- 0.064, P=0.048), and a negative correlation between DACT2 expression levels and fibrosis severity was observed (Spearman rho =-0.476, P=0.010). DACT2 significantly increased the expression levels of KCNE5 and decreased the levels of KCNH2 and SCN5A. Overexpression of DACT2 significantly inhibited the expression of collagen I and collagen III in primary rat atrial fibroblasts. DACT2 could facilitate beta-catenin accumulation by reducing its phosphorylation at Thr41/Ser45 in ILL-1 cells and inhibit the TGF-beta signaling pathway in primary atrial fibroblasts. Conclusions: DACT2 played a role in AF by regulating both structural and electrical atrial remodeling and by affecting beta-catenin accumulation and TGF-beta signaling, and it could serve as a protective factor against AF in valvular heart disease.
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影响因子：
9.3
作者：
Jalife J;Kaur K
通讯作者：
Kaur K
DOI：
--
发表时间：
2007
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Ying Su;Long Zhang;Xia Gao;Fanwei Meng;Jun Wen;Hu Zhou;A. Meng;Ye-Guang Chen
通讯作者：
Ying Su;Long Zhang;Xia Gao;Fanwei Meng;Jun Wen;Hu Zhou;A. Meng;Ye-Guang Chen
影响因子：
4.8
作者：
Su, Ying;Zhang, Long;Chen, Ye-Guang
通讯作者：
Chen, Ye-Guang
影响因子：
20.1
作者：
Verheule, S;Sato, T;Olgin, JE
通讯作者：
Olgin, JE
影响因子：
37.8
作者：
Li, DS;Fareh, S;Nattel, S
通讯作者：
Nattel, S