BOP1 Knockdown Attenuates Neointimal Hyperplasia by Activating p53 and Inhibiting Nascent Protein Synthesis

Abstract

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.

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“…The top 10 KEGG pathways (those enriched in the shortest paths) are shown in Table 6 ( Turi et al, 2019 ; Jia et al, 2021 ; Chothani et al, 2019 ; Yin et al, 2021 ; Manhas and Rath, 2020 ; Li et al, 2018 ; Nakajima et al, 2019 ; Hosseini et al, 2021 ; Critchley et al, 2018 ; Lathe et al, 2014 ; Margiotta, 2021 ; Nickel et al, 2002 ; Chen et al, 2020 ; Luo et al, 2020 ; Miller et al, 2021 ; Stadtman et al, 2005 ; Bonifácio et al, 2021 ; Blachier et al, 2020 ; Kumar et al, 2017 ; Récher, 2021 ; Klemm and Ruland, 2006 ). The most frequently enriched KEGG pathway was “ribosome” (enriched in eight shortest paths; Figure 4A ).…”

“…The most frequently enriched KEGG pathway was “ribosome” (enriched in eight shortest paths; Figure 4A ). The rate of ribosome biogenesis has an important role in cell cycle progression and proliferation, which are closely related to coronary restenosis and atherosclerosis ( Turi et al, 2019 ; Jia et al, 2021 ). Further, RNA translation and RNA transcription in the ribosome participate in fibration, which is vital to the development of atherosclerosis ( Chothani et al, 2019 ).…”

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