Abstract
ABSTRACTIn 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.
Highlights
Vascular smooth muscle cells (VSMCs) are the main components of the vascular wall
The expression of Histone deacetylase 4 (HDAC4), MEG3, miR-125a-5p and interferonregulatoryfactor 1 (IRF1) in VSMCs induced by Platelet derived growth factor (PDGF)-BB
VSMCs were divided into control group and PDGF-BB group, wherein the cells in PDGFBB group were treated with 20 ng/ml of PDGF-BB for 24 h to simulate the abnormal proliferation of VSMCs in intimal hyperplasia (IH)
Summary
Its abnormal proliferation is the major pathological basis for vascular proliferative disorders, such as atherosclerosis, and postangioplasty stenosis, which plays an important role in intimal hyperplasia (IH) [1]. Inhibiting the abnormal proliferation of VSMCs could play a role in alleviating IH. It has been reported that HDAC4 can play an important role in the development of various diseases by participating in biological processes, such as the regulation of gene transcription and cell proliferation [3,4,5]. Ginnan et al [6] found that overexpression of HDAC4 could promote the proliferation of VSMCs, which suggested that VSMCs abnormal proliferation might be inhibited by interfering with the expression of HDAC4. The mechanism of HDAC4 on VSMCs proliferation is not clear
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