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ANO1 regulates cardiac fibrosis via ATI-mediated MAPK pathway
Cell Calcium ( IF 4.3 ) Pub Date : 2020-10-06 , DOI: 10.1016/j.ceca.2020.102306
Xiangqin Tian 1 , Changye Sun 2 , Xianwei Wang 2 , Ketao Ma 3 , Yuqiao Chang 2 , Zhikun Guo 2 , Junqiang Si 3
Affiliation  

Cardiac fibrosis is associated with most of heart diseases, but its molecular mechanism remains unclear. Anoctamin-1 (ANO1), a calcium-activated chloride channels (CaCCs) protein, plays a critical role in various pathophysiological processes. In the current study, we identified ANO1 expression in myocardial infarction (MI) model of rat and verified the role of ANO1 in cardiac fibrosis using transcriptomics combined with RNAi assays. we found that ANO1 expression was increased during the first two weeks, and decreased in the third week after MI. Fluorescence double labeling showed that ANO1 was mainly expressed in cardiac fibroblasts (CFs) and displayed an increased expression in CFs with proliferation tendency. The proliferation and secretion of CFs were markedly inhibited by knockdown of ANO1. RNA-Seq showed that most of the downregulation genes were related to the proliferation of CFs and cardiac fibrosis. After ANO1 knockdown, the expressions of angiotensin II type 1 receptor (AT1R) and cell nuclear proliferation antigen were markedly reduced, and the phosphorylation levels of MEK and ERK1/2 was decreased significantly, indicating that ANO1 regulate cardiac fibrosis through ATIR-mediated MAPK signaling pathway. These findings would be useful for the development of therapeutic strategies targeting ANO1 to treat and prevent cardiac fibrosis.



中文翻译:

ANO1 通过 ATI 介导的 MAPK 通路调节心脏纤维化

心脏纤维化与大多数心脏病有关,但其分子机制尚不清楚。Anoctamin-1 (ANO1) 是一种钙激活的氯离子通道 (CaCCs) 蛋白,在各种病理生理过程中起着关键作用。在目前的研究中,我们确定了 ANO1 在大鼠心肌梗死 (MI) 模型中的表达,并使用转录组学结合 RNAi 分析验证了 ANO1 在心脏纤维化中的作用。我们发现 ANO1 表达在前两周增加,并在 MI 后第三周减少。荧光双标显示ANO1主要在心脏成纤维细胞(CFs)中表达,并在CFs中表达增加并有增殖趋势。ANO1的敲低显着抑制了CF的增殖和分泌。RNA-Seq显示大部分下调基因与CFs的增殖和心脏纤维化有关。ANO1敲低后,血管紧张素II 1型受体(AT1R)和细胞核增殖抗原的表达显着降低,MEK和ERK1/2的磷酸化水平显着降低,表明ANO1通过ATIR介导的MAPK信号调控心脏纤维化途径。这些发现将有助于开发针对 ANO1 的治疗策略,以治疗和预防心脏纤维化。表明 ANO1 通过 ATIR 介导的 MAPK 信号通路调节心脏纤维化。这些发现将有助于开发针对 ANO1 的治疗策略,以治疗和预防心脏纤维化。表明 ANO1 通过 ATIR 介导的 MAPK 信号通路调节心脏纤维化。这些发现将有助于开发针对 ANO1 的治疗策略,以治疗和预防心脏纤维化。

更新日期:2020-10-17
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