Interfering histone deacetylase 4 inhibits the proliferation of vascular smooth muscle cells via regulating MEG3/miR-125a-5p/IRF1

Xiangtao Zheng; Ziheng Wu; Ke Xu; Yihui Qiu; Xiang Su; Zhen Zhang; Mengtao Zhou

doi:10.1080/19336918.2018.1506653

Interfering histone deacetylase 4 inhibits the proliferation of vascular smooth muscle cells via regulating MEG3/miR-125a-5p/IRF1

Cell Adh Migr. 2019 Dec;13(1):41-49. doi: 10.1080/19336918.2018.1506653. Epub 2018 Aug 29.

Authors

Xiangtao Zheng¹, Ziheng Wu², Ke Xu¹, Yihui Qiu¹, Xiang Su¹, Zhen Zhang³, Mengtao Zhou³

Affiliations

¹ a Department of Vascular Surgery , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
² b Department of Vascular Surgery, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China.
³ c Department of Surgery , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.

Abstract

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.

Keywords: HDAC4; IRF1; MEG3; VSMCs; miR-125a-5p.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Becaplermin / pharmacology
Cells, Cultured
Gene Expression Regulation / drug effects*
Histone Deacetylases / chemistry
Histone Deacetylases / genetics
Histone Deacetylases / metabolism*
Interferon Regulatory Factor-1 / antagonists & inhibitors
Interferon Regulatory Factor-1 / genetics
Interferon Regulatory Factor-1 / metabolism*
Male
MicroRNAs / antagonists & inhibitors
MicroRNAs / genetics
MicroRNAs / metabolism*
Muscle, Smooth, Vascular / cytology*
Muscle, Smooth, Vascular / drug effects
Muscle, Smooth, Vascular / metabolism
Neointima / drug therapy
Neointima / pathology*
RNA, Long Noncoding / antagonists & inhibitors
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
Rats
Rats, Sprague-Dawley

Substances

Interferon Regulatory Factor-1
Irf1 protein, rat
MEG3 non-coding RNA, rat
MIRN125 microRNA, rat
MicroRNAs
RNA, Long Noncoding
Becaplermin
HDAC4 protein, rat
Histone Deacetylases

Grants and funding

This work was supported by the National Natural Science Foundation of China (No.81770409; No.81770630), the Natural Science Foundation of Zhejiang Province (No.LY16H020004; No.LY17H020011), Innovative Research Groups of the General Surgery of Wenzhou (No.C20150003) and Science and Technology Project of Wenzhou Science & Technology Bureau (No.Y20170080).