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Nucleolin regulates the proliferation of vascular smooth muscle cells in atherosclerotic via Aurora B
Authors:Hui Sun  Lingjin Huang  Pengfei Liang  Yuting Tang  Cheng Chen  Huan Chen  Xiaofang Lin  Zhengyang Luo  Ying Li  Bimei Jiang  Xianzhong Xiao
Institution:1. Department of Pathophysiology, Sepsis Translational Medicine Key Lab of Hunan Province, Xiangya School of Medicine, Central South University, Hunan, China;2. Department of Cardiothoracic Surgery, Xiangya Hospital Central South University, Hunan, China

Contribution: Formal analysis (equal);3. Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Hunan, China

Contribution: Formal analysis (equal);4. Department of Pathophysiology, Sepsis Translational Medicine Key Lab of Hunan Province, Xiangya School of Medicine, Central South University, Hunan, China

Contribution: Data curation (equal);5. Department of Pathophysiology, Sepsis Translational Medicine Key Lab of Hunan Province, Xiangya School of Medicine, Central South University, Hunan, China

Contribution: Formal analysis (equal);6. Department of Clinical Laboratory, the Second Xiangya Hospital, Central South University, Hunan, China

Contribution: Formal analysis (equal);7. Department of Pathophysiology, Sepsis Translational Medicine Key Lab of Hunan Province, Xiangya School of Medicine, Central South University, Hunan, China

Contribution: Writing - review & editing (equal)

Abstract:Vascular smooth muscle cells (VSMCs) play a significant role in atherosclerosis. As a multifunctional protein, nucleolin (NCL) is involved in many important physiological and pathological processes. In this study, we aimed to investigate the role of nucleolin in VSMCs proliferation and cell cycle. The expression of nucleolin increased in VSMCs of mice with aortas advanced plaques. With the left common carotid-artery ligation-injury model, immunofluorescence staining revealed that nucleolin and Ki67 expression increased in VSMCs in mice left carotid artery compared with right carotid artery after surgery. POVPC or ox-LDL up-regulated nucleolin mRNA and protein expression in a dose- and time-dependent manner in HAVSMCs. POVPC (5μg/ml) or ox-LDL (50μg/ml) promoted the proliferation of HAVSMCs. Nucleolin ablation relieved the pro-proliferation role of VSMCs. The cell cycle assay and cell ability results showing that POVPC or ox-LDL increased the proliferation, but nucleolin ablation inhibited the proliferation of HAVSMCs. And nucleolin ablation can prevent DNA replication at S phase and induce cell cycle arrest in S phase. The bioinformatics database predicts protein-protein interactions with nucleolin and aurora B. Nucleolin overexpression and ablation affected the expression of aurora B. These findings indicate for the first time that nucleolin actively involved the proliferation of VSMCs via aurora B.
Keywords:atherosclerosis  Aurora B  cell cycle  nucleolin  vascular smooth muscle cells
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