Department of Cardiology, Tongren Municipal People's Hospital, Tongren 554300, China.
Department of Cardiology, The Sixth Affiliated Hospital of Jishou University, Jishou 416000, China.
Can J Physiol Pharmacol. 2023 Dec 1;101(12):652-660. doi: 10.1139/cjpp-2022-0549. Epub 2023 Sep 25.
Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.
血管平滑肌细胞（VSMCs）表型转换被认为是 VSMCs 去分化、增殖和迁移能力增强的表现，其中 microRNAs 已被确定为该过程的重要调节因子。本研究旨在探讨 miR-122 对 VSMC 表型调节的病理生理作用。结果表明，血小板衍生生长因子-BB（PDGF-BB）处理的 VSMCs 中发现 miR-122 表达降低。接下来，我们研究了 miR-122 敲低对 PDGF-BB 刺激的 VSMCs 的反应。miR-122 沉默显示出增殖和迁移能力增强，而分化标志物的表达减弱。miR-122 的过表达逆转了上述结果。最后，我们进一步证明 FOXO3 是 miR-122 的重要靶标。综上所述，我们证明 miR-122 沉默通过上调 FOXO3 表达促进 VSMC 表型调节，表明 miR-122 可能是内膜形成的新的治疗靶点。
