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核仁素通过调节 EGF 和 PDGF-BB 促进血管平滑肌细胞 Ang II 诱导的表型转化。

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

机构信息

Department of Cardiology, Xiangya Hospital, Central South University, Changsha, China.

Department of Cardiology, The First Hospital of Changsha, Changsha, China.

出版信息

J Cell Mol Med. 2020 Jan;24(2):1917-1933. doi: 10.1111/jcmm.14888. Epub 2020 Jan 1.

DOI:10.1111/jcmm.14888
PMID:31893573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6991698/
Abstract

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.

摘要

核仁素的 RNA 结合特性在调节细胞生长和增殖中起着基础性作用。我们之前已经表明,核仁素在血管平滑肌细胞(VSMCs)受血管紧张素 II(Ang II)诱导的表型转化中起着重要的调节作用。在本研究中,我们旨在研究核仁素介导的 Ang II 诱导的 VSMCs 表型转化的分子机制。使用表皮生长因子(EGF)和血小板衍生生长因子(PDGF)抑制剂来观察 Ang II 对 VSMCs 表型转化的影响。通过核仁素基因突变、基因过表达和 RNA 干扰技术鉴定核仁素在 VSMCs 表型转化中的调节作用。此外,我们阐明了核仁素对 VSMCs 表型转化的调节作用的分子机制。EGF 和 PDGF-BB 在 Ang II 诱导的 VSMCs 表型转化中起重要作用。核仁素对 EGF 和 PDGF-BB 的表达和分泌具有正向调节作用。此外,核仁素可以与 EGF 和 PDGF-BB mRNA 的 5'非翻译区(UTR)结合,这种结合上调了 EGF 和 PDGF-BB mRNA 的稳定性和表达,促进了 Ang II 诱导的 VSMCs 表型转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/9bee327972c8/JCMM-24-1917-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/bbc70d8ceb3f/JCMM-24-1917-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/47930c64f69c/JCMM-24-1917-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/d13f0f0bf0fd/JCMM-24-1917-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/2177ee91e04b/JCMM-24-1917-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/40afad60ab90/JCMM-24-1917-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/99f9e59a1740/JCMM-24-1917-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/9bee327972c8/JCMM-24-1917-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/bbc70d8ceb3f/JCMM-24-1917-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/47930c64f69c/JCMM-24-1917-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/d13f0f0bf0fd/JCMM-24-1917-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/2177ee91e04b/JCMM-24-1917-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/40afad60ab90/JCMM-24-1917-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/99f9e59a1740/JCMM-24-1917-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79b/6991698/9bee327972c8/JCMM-24-1917-g007.jpg

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