Zeng Ni, Wen Yi-Hong, Pan Rong, Yang Jing, Yan Yu-Min, Zhao An-Zhi, Zhu Jie-Ning, Fang Xian-Hong, Shan Zhi-Xin
School of Medicine, South China University of Technology, Guangzhou, 510632, China.
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510632, China.
J Cardiovasc Transl Res. 2021 Dec;14(6):1051-1062. doi: 10.1007/s12265-021-10116-w. Epub 2021 Mar 15.
Increasing evidence has shown that microRNAs (miRNAs) participate in cardiac fibrosis. We aimed to elucidate the effect of miRNA miR-25-3p on cardiac fibrosis. MiRNA microarray was used to profile miRNAs in the myocardium of angiotensin-II (Ang-II)-infused mice. Effect of miR-25-3p on expression of fibrosis-related genes, including Col1a1, Col3a1, and Acta2, was investigated both in vitro and in vivo. MiR-25-3p was shown increased in the myocardium of Ang-II-infused mice and patients with heart failure. MiR-25-3p enhanced fibrosis-related gene expression in mouse cardiac fibroblasts (mCFs) and in the myocardium of Ang-II-infused mice. Dickkopf 3 (Dkk3) was identified as a target gene of miR-25-3p, and Dkk3 could ameliorate Smad3 activation and fibrosis-related gene expression via enhancing Smad7 expression in mCFs. Additionally, NF-κB signal was proven to mediate upregulation of miR-25-3p in cardiac fibrosis. Our findings suggest that miR-25-3p enhances cardiac fibrosis by suppressing Dkk3 to activate Smad3 and fibrosis-related gene expression.
越来越多的证据表明，微小RNA（miRNA）参与心脏纤维化。我们旨在阐明miRNA miR-25-3p对心脏纤维化的影响。使用miRNA微阵列分析血管紧张素II（Ang-II）灌注小鼠心肌中的miRNA。在体外和体内研究了miR-25-3p对包括Col1a1、Col3a1和Acta2在内的纤维化相关基因表达的影响。结果显示，在Ang-II灌注小鼠和心力衰竭患者的心肌中，miR-25-3p有所增加。miR-25-3p增强了小鼠心脏成纤维细胞（mCFs）和Ang-II灌注小鼠心肌中纤维化相关基因的表达。Dickkopf 3（Dkk3）被鉴定为miR-25-3p的靶基因，Dkk3可通过增强mCFs中Smad7的表达来改善Smad3激活和纤维化相关基因的表达。此外，已证实NF-κB信号介导心脏纤维化中miR-25-3p的上调。我们的研究结果表明，miR-25-3p通过抑制Dkk3来激活Smad3和纤维化相关基因的表达，从而增强心脏纤维化。
