miR‐141‐3p is proven to play a prominent role in various inflammation‐related diseases. Nonetheless, little is known concerning the function of miR‐141‐3p in vascular smooth muscle cells (VSMCs) dysfunction and the underlying mechanism. ApoE knockdown (ApoE−/−) C57BL/6 mice and human VSMCs were employed to establish atherosclerosis (AS) animal model and cell model, respectively. The expressions of miR‐141‐3p and Keap1 mRNA were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Enzyme‐linked immunosorbent assay (ELISA) was conducted to determine inflammatory cytokines IL‐6, IL‐β and TNF‐α. Cell proliferation, migration and apoptosis were analyzed by BrdU assay, Transwell assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Luciferase reporter assay was carried out to determine the regulatory relationship between miR‐141‐3p and Keap1. Additionally, Western blot was used to detect the function of miR‐141‐3p on the expression levels of Keap1, Nrf2 and HO‐1 in VSMCs. miR‐141‐3p was remarkably down‐regulated in both AS animal model and cell model while the expression of Keap1 was elevated. Proliferation and migration of VSMCs were suppressed after miR‐141‐3p mimics transfection and cell apoptosis was promoted. miR‐141‐3p also inhibited the expressions of IL‐6, IL‐β, TNF‐α and Keap1 but promoted the expressions of Nrf2 and HO‐1. Moreover, the binding site between miR‐141‐3p and the 3′UTR of Keap1 was confirmed. miR‐141‐3p is down‐regulated during AS, and it can alleviate VSMCs' dysfunction by targeting the Keap1/Nrf2/HO‐1 axis.

中文翻译：

---

miR-141-3p通过调节Keap1/Nrf2/HO-1通路抑制血管平滑肌细胞增殖和迁移

miR-141-3p 已被证明在各种炎症相关疾病中发挥着重要作用。尽管如此，关于 miR-141-3p 在血管平滑肌细胞 (VSMCs) 功能障碍中的功能及其潜在机制知之甚少。ApoE敲低（ApoE-/-）C57BL/6小鼠和人VSMC分别用于建立动脉粥样硬化（AS）动物模型和细胞模型。通过定量实时聚合酶链反应（qRT-PCR）检测 miR-141-3p 和 Keap1 mRNA 的表达。进行酶联免疫吸附试验 (ELISA) 以测定炎性细胞因子 IL-6、IL-β 和 TNF-α。分别通过BrdU测定、Transwell测定和末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)测定分析细胞增殖、迁移和凋亡。进行荧光素酶报告基因检测以确定 miR-141-3p 和 Keap1 之间的调控关系。此外，Western blot检测miR-141-3p对VSMCs中Keap1、Nrf2和HO-1表达水平的影响。miR-141-3p在AS动物模型和细胞模型中均显着下调，而Keap1的表达升高。miR-141-3p模拟物转染后VSMCs增殖和迁移受到抑制，促进细胞凋亡。miR-141-3p 还抑制 IL-6、IL-β、TNF-α 和 Keap1 的表达，但促进 Nrf2 和 HO-1 的表达。此外，证实了 miR-141-3p 与 Keap1 的 3'UTR 之间的结合位点。miR-141-3p 在 AS 期间下调，它可以通过靶向 Keap1/Nrf2/HO-1 轴缓解 VSMC 的功能障碍。