MiR-324-3p Regulates Fibroblast Proliferation via Targeting TGF-β1 in Atrial Fibrillation.
MiR-324-3p Regulates Fibroblast Proliferation via Targeting TGF-β1 in Atrial Fibrillation.
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DOI：
10.1536/ihj.20-423
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发表时间：
2020-11
影响因子：
1.5
通讯作者：
Jiali Xu;Sisi Lei;Shuo Sun;Wei Zhang;Feiyu Zhu;H. Yang;Qing-mei Xu;Bing Zhang;Hui Li-Hui-L
中科院分区：
文献类型：
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作者：
Jiali Xu;Sisi Lei;Shuo Sun;Wei Zhang;Feiyu Zhu;H. Yang;Qing-mei Xu;Bing Zhang;Hui Li-Hui-L
心房颤动（AF）是临床常见的心律失常之一，目前缺乏有效的治疗手段。心脏成纤维细胞在心肌纤维化和心脏重塑中起重要作用，这与AF进展有关。据报道，MicroRNAs（miRNAs）参与了AF心肌纤维化的调控，但miR-324- 3 p是否参与了AF心肌纤维化的发生，以及miR-324- 3 p调控AF心肌成纤维细胞的初步分子机制尚不清楚。在本研究中，发现AF患者和AF大鼠模型中miR-324- 3 p减少。接下来，我们通过miR-324 - 3 p过表达研究了miR-324 - 3 p对心肌成纤维细胞增殖的影响，发现miR-324- 3 p在体外抑制成纤维细胞增殖。此外，我们还发现miR-324- 3 p直接靶向转化生长因子β1，可能参与了AF心肌纤维化的发生。同时，miR-324- 3 p模拟物处理抑制了成纤维细胞中PI 3 K/AKT信号通路。这些结果揭示了miR-324- 3 p在体外调控成纤维细胞增殖的分子机制，为临床治疗房颤提供了新的思路。
Atrial fibrillation (AF), one of the common clinical arrhythmias, lacks effective treatment manners. Cardiac fibroblasts play an essential role in myocardial fibrosis and cardiac remodeling, which are involved in AF progression. Reportedly, MicroRNAs (miRNAs) regulate the myocardial fibrosis in AF. However, whether miR-324-3p involves myocardial fibrosis in AF and the tentative molecular mechanisms of miR-324-3p regulating cardiac fibroblasts during AF remains unknown. In the present study, miR-324-3p was found to be decreased in patients with AF and AF rat model. Next, we investigated the effect of miR-324-3p on myocardial fibroblast proliferation through miR-324-3p overexpression and found that miR-324-3p inhibited fibroblast proliferation in vitro. Furthermore, we found that miR-324-3p directly targeted transforming growth factor β1 in fibroblast, which may be involved in the development of myocardial fibrosis during AF. Meanwhile, miR-324-3p mimics treatment suppressed the PI3K/AKT signaling pathway in fibroblast. These results demonstrated a molecular mechanism of miR-324-3p regulating fibroblast proliferation in vitro, which might provide a novel potential treatment manner in AF in clinic.