MicroRNA-29a suppresses cardiac fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway.
MicroRNA-29a suppresses cardiac fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway.
复制标题
DOI：
10.1016/j.ijbiomac.2016.04.010
复制
发表时间：
2016-07
影响因子：
8.2
通讯作者：
Hui Tao;Ze-Wen Chen;Jing-jing Yang;Kai-Hu Shi
中科院分区：
文献类型：
--
作者：
Hui Tao;Ze-Wen Chen;Jing-jing Yang;Kai-Hu Shi
心脏成纤维细胞增殖是心脏纤维化最重要的病理生理特征，但其机制尚不完全清楚。微小RNA（miRNA）通过结合特定位点来调节基因表达。研究表明，miRNA-29 a在心肌纤维化中起关键作用。VEGF-A通过MAPK信号通路在心肌纤维化中发挥作用。现有证据预测VEGF-A是miRNA-29 a的潜在靶点之一。因此，我们探索miRNA-29 a及其潜在靶点VEGF-A在心脏纤维化中的作用。在我们的研究中，在心脏纤维化组织中，miRNA-29 a下调，而VEGF-A上调。转染miRNA-29 a抑制剂的大鼠心肌成纤维细胞显示miRNA-29 a低表达，VEGF-A蛋白和mRNA表达增强。然而，用miRNA-29 a模拟物转染的心脏成纤维细胞获得了相反的表达结果。此外，miRNA-29 a的过表达抑制心脏成纤维细胞增殖。结论：miRNA-29 a通过靶向VEGF-A/MAPK信号通路抑制心肌纤维化和成纤维细胞增殖，提示miRNA-29 a可能在心肌纤维化的治疗中发挥作用。
Cardiac fibroblasts proliferation is the most important pathophysiological character of cardiac fibrosis while the underlying mechanisms are still incompletely known. MicroRNAs (miRNAs) regulate gene expression by binding to specific sites. Studies have been indicated that miRNA-29a play a key role in cardiac fibrosis. VEGF-A carries out its functions through MAPK signaling pathway in cardiac fibrosis. Existing proofs predict that the VEGF-A is one of the potential targets of miRNA-29a. We therefore probe the role of miRNA-29a and its latent target VEGF-A during cardiac fibrosis. In our study, miRNA-29a was down-regulated while VEGF-A was up-regulated in cardiac fibrosis tissues. The rat cardiac fibroblasts that were transfected with miRNA-29a inhibitor exhibited low-expression of miRNA-29a, enhanced VEGF-A protein and mRNA expression. Nevertheless, the cardiac fibroblasts transfected with miRNA-29a mimics obtained the opposite expression result. Furthermore, over-expression of miRNA-29a suppresses cardiac fibroblasts proliferation. In conclusion, these results suggested that miRNA-29a suppresses cardiac fibrosis and fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway implicating that miRNA-29a might play a role in the treatment of cardiac fibrosis.