Department of Pathology, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, And Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, And Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Exp Cell Res. 2022 Oct 1;419(1):113303. doi: 10.1016/j.yexcr.2022.113303. Epub 2022 Aug 5.
Angiotensin II (Ang II) plays a central role in vascular smooth muscle cell (VSMC) proliferation and migration, being key to regulate vascular function and promote vascular remodeling in cardiovascular diseases. We recently showed that miR-31-5p promoted oxidative stress in spontaneously hypertensive rats. In this study, we aim to investigate whether miR-31-5p and fibronectin type III domain-containing 5 (FNDC5) contribute to Ang II-induced VSMC proliferation and migration. Experiments were performed in primary VSMCs of wide-type (WT) and FNDC5 mice as well as the rat A7r5 cell line. We found that Ang II increased miR-31-5p level, reduced FNDC5 expression and stimulated VSMC proliferation and migration, which were aggravated by miR-31-5p mimic, and prevented by miR-31-5p inhibitor in VSMCs. The Ang II-induced VSMC proliferation were prevented by exogenous FNDC5 in both WT and FNDC5 mice, while the effects were more significant in FNDC5 mice. Furthermore, exogenous FNDC5 reversed the effects of miR-31-5p mimic on VSMC proliferation and migration in Ang II-treated VSMCs. Meanwhile, FNDC5 deficiency prevented the effects of miR-31-5p inhibitor on VSMC proliferation and migration in Ang II-treated VSMCs. In conclusion, our findings demonstrate that the miR-31-5p upregulation and the following FNDC5 downregulation contribute to Ang II-induced VSMC proliferation and migration.
血管紧张素 II（Ang II）在血管平滑肌细胞（VSMC）增殖和迁移中发挥核心作用，是调节血管功能和促进心血管疾病血管重塑的关键。我们最近表明，miR-31-5p 促进自发性高血压大鼠的氧化应激。在这项研究中，我们旨在研究 miR-31-5p 和纤连蛋白 III 型结构域包含 5（FNDC5）是否有助于 Ang II 诱导的 VSMC 增殖和迁移。实验在 WT 和 FNDC5 小鼠的原代 VSMC 以及大鼠 A7r5 细胞系中进行。我们发现 Ang II 增加了 miR-31-5p 水平，降低了 FNDC5 表达，并刺激了 VSMC 增殖和迁移，miR-31-5p 模拟物加剧了这些作用，而 miR-31-5p 抑制剂则在 VSMC 中阻止了这些作用。外源性 FNDC5 在 WT 和 FNDC5 小鼠中均阻止了 Ang II 诱导的 VSMC 增殖，而在 FNDC5 小鼠中作用更显著。此外，外源性 FNDC5 逆转了 miR-31-5p 模拟物对 Ang II 处理的 VSMC 中 VSMC 增殖和迁移的影响。同时，FNDC5 缺乏可预防 Ang II 处理的 VSMC 中 miR-31-5p 抑制剂对 VSMC 增殖和迁移的影响。总之，我们的研究结果表明，miR-31-5p 的上调和随后的 FNDC5 下调有助于 Ang II 诱导的 VSMC 增殖和迁移。
