Author:
Chen Tai-Qiang,Guo Xian,Huo Bo,Zhong Xiao-Xuan,Wang Qun-Hui,Chen Yue,Zhu Xue-Hai,Feng Gao-Ke,Jiang Ding-Sheng,Fang Ze-Min,Wei Xiang
Abstract
AbstractThe behavior of vascular smooth muscle cells (VSMCs) contributes to the formation of neointima. We previously found that EHMT2 suppressed autophagy activation in VSMCs. BRD4770, an inhibitor of EHMT2/G9a, plays a critical role in several kinds of cancers. However, whether and how BRD4770 regulates the behavior of VSMCs remain unknown. In this study, we evaluate the cellular effect of BRD4770 on VSMCs by series of experiments in vivo and ex vivo. We demonstrated that BRD4770 inhibited VSMCs’ growth by blockage in G2/M phase in VSMCs. Moreover, our results demonstrated that the inhibition of proliferation was independent on autophagy or EHMT2 suppression which we previous reported. Mechanistically, BRD4770 exhibited an off-target effect from EHMT2 and our further study reveal that the proliferation inhibitory effect by BRD4770 was associated with suppressing on SUV39H2/KTM1B. In vivo, BRD4770 was also verified to rescue VIH. Thus, BRD4770 function as a crucial negative regulator of VSMC proliferation via SUV39H2 and G2/M cell cycle arrest and BRD4770 could be a molecule for the therapy of vascular restenosis.
Funder
Hubei Province health and Family Planning Scientific Research Project
Natural Science Foundation of Hubei Province
National Key R&D Program of China-Key Project for R&D of Digital Diagnosis and Treatment Equipment
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology