Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p.
Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p.
复制标题
IgE 升高通过抑制 miR-486a-5p 促进心脏纤维化
作者：
Zhao H;Yang H;Geng C;Chen Y;Tang Y;Li Z;Pang J;Shu T;Nie Y;Liu Y;Jia K;Wang J
依据：心脏纤维化是心脏重塑的重要特征，也是心力衰竭的标志。最近的研究表明，IgE升高在病理性心脏重塑中起着因果作用。然而，IgE如何促进心脏纤维化的潜在机制尚未完全阐明。方法和结果：为探讨IgE在心脏纤维化中的作用，我们用IgE刺激小鼠原代心脏成纤维细胞（CFs），发现IgE受体（FcεR1）和纤维化相关蛋白在IgE刺激后均增加。CF中FcεR1的特异性缺失减轻了血管紧张素II（Ang II）诱导的小鼠心脏纤维化。为了研究IgE介导的心脏纤维化的潜在机制，进行了深度miRNA-seq。生物信息学和信号通路分析显示，IgE通过抑制miR-486 a-5 p上调CFs中Col 1a 1和Col 3a 1的表达，Smad 1参与了这一过程。发现慢病毒介导的miR-486 a-5 p过表达可减轻Ang II诱导的小鼠心肌间质纤维化。此外，心力衰竭患者血清中miR-486- 5 p水平低于健康对照组，且与NT-proBNP水平呈负相关。结论：我们的研究表明，IgE升高通过调节miR-486 a-5 p和下游因子（如Smad 1）促进病理性心脏纤维化。这些发现为病理性心脏纤维化干预提供了新的靶点。
Rationale: Cardiac fibrosis is an important feature of cardiac remodeling and is a hallmark of heart failure. Recent studies indicate that elevated IgE plays a causal role in pathological cardiac remodeling. However, the underlying mechanism of how IgE promotes cardiac fibrosis has not been fully elucidated. Methods and Results: To explore the function of IgE in cardiac fibrosis, we stimulated mouse primary cardiac fibroblasts (CFs) with IgE and found that both IgE receptor (FcεR1) and fibrosis related proteins were increased after IgE stimulation. Specific deletion of FcεR1 in CFs alleviated angiotensin II (Ang II)-induced cardiac fibrosis in mice. To investigate the mechanisms underlying the IgE-mediated cardiac fibrosis, deep miRNA-seq was performed. Bioinformatics and signaling pathway analysis revealed that IgE upregulated Col1a1 and Col3a1 expression in CFs by repressing miR-486a-5p, with Smad1 participating downstream of miR-486a-5p in this process. Lentivirus-mediated overexpression of miR-486a-5p was found to alleviate Ang II-induced myocardial interstitial fibrosis in mice. Moreover, miR-486-5p serum levels were lower in patients with heart failure than in healthy controls, and were negatively correlated with NT-proBNP levels. Conclusions: Our study demonstrates that elevated IgE promotes pathological cardiac fibrosis by modulating miR-486a-5p and downstream factors, such as Smad1. These findings suggest new targets for pathological cardiac fibrosis intervention.
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DOI：
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发表时间：
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MOUSE EMBRYOGENESIS: METHODS AND PROTOCOLS
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