Nucleolin promotes Ang II-induced phenotypic transformation of vascular smooth muscle cells by regulating EGF and PDGF-BB

被引:13
作者
Fang, Li [1 ,2 ]
Wang, Kang-Kai [3 ]
Zhang, Peng-Fei [4 ]
Li, Tao [3 ]
Xiao, Zhi-Lin [5 ]
Yang, Mei [5 ]
Yu, Zai-Xin [1 ]
机构
[1] Cent S Univ, Xiangya Hosp, Dept Cardiol, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China
[2] First Hosp Changsha, Dept Cardiol, Changsha, Hunan, Peoples R China
[3] Cent S Univ, Xiangya Sch Med, Dept Pathophysiol, Changsha, Hunan, Peoples R China
[4] Cent S Univ, Xiangya Hosp, Key Lab Canc Prote Chinese Minist Hlth, Changsha, Hunan, Peoples R China
[5] Cent S Univ, Xiangya Hosp, Dept Geriatr Cardiol, Changsha, Hunan, Peoples R China
基金
湖南省自然科学基金;
关键词
angiotensin II; EGF; nucleolin; PDGF-BB; phenotypic transformation; vascular smooth muscle cells; GROWTH-FACTOR; RECEPTOR INHIBITION; PROLIFERATION; MIGRATION; STABILIZATION; MECHANISMS; PROTEINS; CANCER;
D O I
10.1111/jcmm.14888
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
RNA-binding properties of nucleolin play a fundamental role in regulating cell growth and proliferation. We have previously shown that nucleolin plays an important regulatory role in the phenotypic transformation of vascular smooth muscle cells (VSMCs) induced by angiotensin II (Ang II). In the present study, we aimed to investigate the molecular mechanism of nucleolin-mediated phenotypic transformation of VSMCs induced by Ang II. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) inhibitors were used to observe the effect of Ang II on phenotypic transformation of VSMCs. The regulatory role of nucleolin in the phenotypic transformation of VSMCs was identified by nucleolin gene mutation, gene overexpression and RNA interference technology. Moreover, we elucidated the molecular mechanism underlying the regulatory effect of nucleolin on phenotypic transformation of VSMCs. EGF and PDGF-BB played an important role in the phenotypic transformation of VSMCs induced by Ang II. Nucleolin exerted a positive regulatory effect on the expression and secretion of EGF and PDGF-BB. In addition, nucleolin could bind to the 5 ' untranslated region (UTR) of EGF and PDGF-BB mRNA, and such binding up-regulated the stability and expression of EGF and PDGF-BB mRNA, promoting Ang II-induced phenotypic transformation of VSMCs.
引用
收藏
页码:1917 / 1933
页数:17
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