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

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 pres...

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Veröffentlicht in:Journal of cellular and molecular medicine 2020-01, Vol.24 (2), p.1917-1933
Hauptverfasser: Fang, Li, Wang, Kang‐Kai, Zhang, Peng‐Fei, Li, Tao, Xiao, Zhi‐Lin, Yang, Mei, Yu, Zai‐Xin
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container_end_page 1933
container_issue 2
container_start_page 1917
container_title Journal of cellular and molecular medicine
container_volume 24
creator Fang, Li
Wang, Kang‐Kai
Zhang, Peng‐Fei
Li, Tao
Xiao, Zhi‐Lin
Yang, Mei
Yu, Zai‐Xin
description 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.
doi_str_mv 10.1111/jcmm.14888
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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.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.14888</identifier><identifier>PMID: 31893573</identifier><language>eng</language><publisher>England: John Wiley &amp; Sons, Inc</publisher><subject>5' Untranslated Regions ; 5' Untranslated Regions - genetics ; Angiotensin ; Angiotensin II ; Angiotensin II - pharmacology ; Antibiotics ; Becaplermin - genetics ; Becaplermin - metabolism ; Bioinformatics ; Biotechnology ; Cell culture ; Cell division ; Cell growth ; Cell Line ; Cell Line, Transformed ; EGF ; Enzymes ; Epidermal growth factor ; Epidermal Growth Factor - genetics ; Epidermal Growth Factor - metabolism ; Gene Expression Regulation ; Genes ; Genes, Reporter ; Genetic transformation ; Genomes ; Genotype &amp; phenotype ; Luciferases - metabolism ; Monoclonal antibodies ; mRNA ; Muscle, Smooth, Vascular - cytology ; Muscles ; Myocytes, Smooth Muscle - metabolism ; Nucleolin ; Original ; PDGF‐BB ; Phenotype ; phenotypic transformation ; Phosphoproteins - metabolism ; Plasmids ; Platelet-derived growth factor ; Point mutation ; Polyclonal antibodies ; Protein Binding ; Proteins ; Regulation ; RNA Stability ; RNA-Binding Proteins - metabolism ; RNA-mediated interference ; Smooth muscle ; Studies ; vascular smooth muscle cells</subject><ispartof>Journal of cellular and molecular medicine, 2020-01, Vol.24 (2), p.1917-1933</ispartof><rights>2019 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley &amp; Sons Ltd</rights><rights>2019 The Authors. 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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. 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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.</abstract><cop>England</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>31893573</pmid><doi>10.1111/jcmm.14888</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-9487-2376</orcidid><orcidid>https://orcid.org/0000-0002-1076-7729</orcidid><oa>free_for_read</oa></addata></record>
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subjects 5' Untranslated Regions
5' Untranslated Regions - genetics
Angiotensin
Angiotensin II
Angiotensin II - pharmacology
Antibiotics
Becaplermin - genetics
Becaplermin - metabolism
Bioinformatics
Biotechnology
Cell culture
Cell division
Cell growth
Cell Line
Cell Line, Transformed
EGF
Enzymes
Epidermal growth factor
Epidermal Growth Factor - genetics
Epidermal Growth Factor - metabolism
Gene Expression Regulation
Genes
Genes, Reporter
Genetic transformation
Genomes
Genotype & phenotype
Luciferases - metabolism
Monoclonal antibodies
mRNA
Muscle, Smooth, Vascular - cytology
Muscles
Myocytes, Smooth Muscle - metabolism
Nucleolin
Original
PDGF‐BB
Phenotype
phenotypic transformation
Phosphoproteins - metabolism
Plasmids
Platelet-derived growth factor
Point mutation
Polyclonal antibodies
Protein Binding
Proteins
Regulation
RNA Stability
RNA-Binding Proteins - metabolism
RNA-mediated interference
Smooth muscle
Studies
vascular smooth muscle cells
title Nucleolin promotes Ang II‐induced phenotypic transformation of vascular smooth muscle cells by regulating EGF and PDGF‐BB
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