In this study, we investigated the role ofhistone deacetylase 4 (HDAC4) and MEG3/miR-125a-5p/interferonregulatoryfactor 1 (IRF1) on vascular smooth muscle cell (VSMCs)proliferation. Platelet derived growth factor (PDGF)-BB was used toinduce the proliferation and migration of VSMCs. The expressionsof MEG3, miR-125a-5p, HDAC4 and IRF1in VSMCs were detectedby qRT-PCR and western blot, respectively. ChIP assay was usedto determine the relationship between MEG3 and HDAC4. Doubleluciferase reporter assay was used to test the regulation betweenmiR-125-5p and IRF1. Results showed that PDGF-BB decreasedthe expression of MEG3 and IRF1, while increased the expressionof miR-125a-5p and HDAC4. In addition, HDAC4 knockdowninhibited the proliferation and migration of VSMCs via upregulatingMEG3 and downregulating miR-125a-5p. MiR-125a-5p inhibitorcould repress the proliferation and migration of VSMCs andalleviate intimal hyperplasia (IH) by directly upregulating IRF1expression. These results suggested that HDAC4 interferenceinhibited PDGF-BB-induced VSMCs proliferation via regulatingMEG3/miR-125a-5p/IRF1 axis, and then alleviated IH.

中文翻译：

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干扰组蛋白脱乙酰基酶4通过调节MEG3 / miR-125a-5p / IRF1抑制血管平滑肌细胞的增殖。

在这项研究中，我们调查了组蛋白脱乙酰基酶4（HDAC4）和MEG3 / miR-125a-5p /干扰素调节因子1（IRF1）在血管平滑肌细胞（VSMC）增殖中的作用。血小板衍生生长因子（PDGF）-BB被用于诱导VSMC的增殖和迁移。分别通过qRT-PCR和western blot检测MEG3，miR-125a-5p，HDAC4和IRF1在VSMC中的表达。用ChIP测定法确定MEG3和HDAC4之间的关系。采用双荧光素酶报告基因检测法检测miR-125-5p和IRF1之间的调控。结果表明，PDGF-BB降低了MEG3和IRF1的表达，同时增加了miR-125a-5p和HDAC4的表达。此外，HDAC4敲低通过上调MEG3和下调miR-125a-5p抑制VSMC的增殖和迁移。MiR-125a-5p抑制剂可通过直接上调IRF1的表达来抑制VSMC的增殖和迁移并减轻内膜增生（IH）。这些结果表明，HDAC4干扰通过调节MEG3 / miR-125a-5p / IRF1轴抑制PDGF-BB诱导的VSMC增殖，然后减轻IH。