Open AccessBOP1 Knockdown Attenuates Neointimal Hyperplasia by Activating p53 and Inhibiting Nascent Protein Synthesis
Author(s) -
Fangyuan Jia,
Qi Wu,
Zhiwei Wang,
Min Zhang,
Shenfang Yuan,
Yanjia Che,
Bowen Li,
Zhipeng Hu,
Xiaoping Hu
Publication year - 2021
Publication title -
oxidative medicine and cellular longevity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.494
H-Index - 93
eISSN - 1942-0900
pISSN - 1942-0994
DOI - 10.1155/2021/5986260
Subject(s) - gene knockdown , ribosome biogenesis , neointimal hyperplasia , microbiology and biotechnology , cell growth , nucleolus , biology , chemistry , medicine , cancer research , restenosis , cell culture , ribosome , rna , biochemistry , cytoplasm , gene , genetics , stent
The rate of ribosome biogenesis plays a vital role in cell cycle progression and proliferation and is strongly connected with coronary restenosis and atherosclerosis. Blocking of proliferation 1 (BOP1) has been found as an evolutionarily conserved gene and a pivotal regulator of ribosome biogenesis and cell proliferation. However, little is known about its role in neointimal formation and its relationship with vascular smooth muscle cell (VSMC) proliferation and migration. The present study mainly explores the effect of BOP1 on VSMCs, the progression of neointimal hyperplasia, and the pathogenic mechanism. The expression of BOP1 was found to be significantly elevated during neointimal formation in human coronary samples and the rat balloon injury model. BOP1 knockdown inspires the nucleolus stress, which subsequently activates the p53-dependent stress response pathway, and inhibits the nascent protein synthesis, which subsequently inhibits the proliferation and migration of VSMCs. Knockdown ribosomal protein L11 (RPL11) by transfecting with siRNA or inhibiting p53 by pifithrin- α (PFT- α ) partly reserved the biological effects induced by BOP1 knockdown. The present study revealed that BOP1 deletion attenuates VSMC proliferation and migration by activating the p53-dependent nucleolus stress response pathway and inhibits the synthesis of nascent proteins. BOP1 may become a novel biological target for neointimal hyperplasia.