Atorvastatin Calcium Inhibits PDGF-ββ-Induced Proliferation and Migration of VSMCs Through the G0/G1 Cell Cycle Arrest and Suppression of Activated PDGFRβ-PI3K-Akt Signaling Cascade

Chen, Shuang; Dong, Siyuan; Zhao, Li; Guo, Xiaofan; Zhang, Naijin; Yu, Bo; Sun, Yingxian

doi:10.1159/000484648

Cited by 21 publications

(14 citation statements)

References 44 publications

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“…KLF4 is the downstream target of ERK1/2 in the PDGF-BB-induced signaling pathway ( 27 , 28 ). Consistent with another study ( 29 ), we noted that PDGF-BB induces phosphorylation of ERK1/2 and elevated KLF4 expression in VSMCs. Moreover, crocin treatment significantly inhibited PDGF-BB-induced activation of ERK/KLF4 signaling pathway.…”

Section: Discussionsupporting

confidence: 93%

Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch

Tong

2018

Mol Med Report

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The phenotypic switch of vascular smooth muscle cells (VSMCs) is a major initiating factor for atherosclerotic cardiovascular diseases. Platelet-derived growth factor-BB (PDGF-BB) initiates a number of biological processes that contribute to VSMC proliferation and phenotypic switch. Crocin, a component of saffron, has been reported to inhibit atheromatous plaque formation. However, the effects of crocin on PDGF-BB-induced VSMC proliferation and phenotypic switch remain unclear. The aim of the present study was to investigate the role of crocin on PDGF-BB-induced VSMCs proliferation and phenotypic switch and its underlying mechanisms. Cell proliferation and markers of VSMCs phenotypic switch were measured using a Cell Counting Kit-8 assay and western blot analysis, respectively. The signaling pathways involved in the effects of crocin on VSMCs were validated by western blot analysis with or without the use of specific pathway inhibitors. Crocin significantly inhibited PDGF-BB-induced VSMCs proliferation compared with the PDGF-BB only group (P<0.05). In addition, crocin significantly abrogated the PDGF-BB-induced increase in contractile protein α-smooth muscle actin, calponin and decrease in synthetic proteins osteopontin (OPN) in a concentration dependent manner (P<0.05). In addition, crocin slowed PDGF-BB-induced Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK)/Kruppel-like factor 4 (KLF4) signaling activation in VSMCs. By applying the JAK inhibitor (AG490) and ERK1/2 inhibitor (U0126), the results suggested that the crocin inhibited PDGF-BB-induced VSMCs phenotypic switch through the JAK/STAT3 and ERK/KLF4 signaling pathways. These results suggested that crocin may effectively prevent PDGF-BB-induced VSMCs proliferation and phenotypic switch and may be a promising candidate for the therapy of atherosclerotic cardiovascular diseases.

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Section: Discussionsupporting

confidence: 93%

Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch

Tong

2018

Mol Med Report

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“…The analysis results suggested that nucleolin bound to the mRNA of these genes, regulated the expressions of these phenotype‐related genes and then modulated the phenotypic transformation of VSMCs. Recent studies have shown that EGF and PDGF‐BB play a key regulatory role in phenotype transformation of VSMCs . Therefore, we speculated that nucleolin might bind to the mRNA of EGF and PDGF‐BB, regulate the expressions and the stability of EGF and PDGF mRNA and then positively modulate the phenotypic transformation of VSMCs.…”

Section: Resultsmentioning

confidence: 96%

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

Wang

Zhang

et al. 2020

J Cellular Molecular Medi

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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.

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“…Some pathways regulate the alteration of VSMC phenotype [32–34]. Multiple studies have proved that Sirt1/NF-κB axis participates in the alteration of phenotype of VSMCs [35–37].…”

Section: Discussionmentioning

confidence: 99%

Phenotype of Vascular Smooth Muscle Cells (VSMCs) Is Regulated by miR-29b by Targeting Sirtuin 1

2018

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BACKGROUND Phenotypic switch of vascular smooth muscle cells (VSMCs) participates in the etiology of various vascular diseases. It has been proved that microRNAs (miRNAs) serve as crucial regulators of functions of VSMCs. This study aimed to discover how miR-29b regulates the transformation of VSMCs phenotypes in mice. MATERIAL AND METHODS Primary VSMCs of aorta in mice were cultured in DMEM medium. A series of experiments involving transfection of oligonucleotides in cultured VSMCs, quantitative reverse transcription PCR (qRT-PCR), luciferase reporter assay, and Western blotting analysis were performed in this study. RESULTS We found that in VSMCs cultured in presence of stimulator, platelet-derived growth factor-BB (PDGF-BB), miR-29b was upregulated significantly and expressions of VSMC-phenotype-related genes (α-SMA, calponin, and SM-MHC) were regulated by miR-29b. Moreover, through downregulation of sirtuin 1 (SIRT1), miR-29b affects phenotypic transformation of VSMCs. Luciferase report assay identified a significant increase of SIRT1 3'-UTR activity in treatment with miR-29b inhibitor, which, however, was reversed in the presence of miR-29b mimic. Suppression of miR-29b reversed the activation of NF-κB induced by PDGF-BB in VSMCs. CONCLUSIONS We concluded that miR-29b is an important regulator in the PDGF-BB-mediated VSMC phenotypic transition by targeting SIRT1. Interventions aimed at miR-29b may be promising in treating numerous proliferative vascular disorders.

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Atorvastatin Calcium Inhibits PDGF-ββ-Induced Proliferation and Migration of VSMCs Through the G0/G1 Cell Cycle Arrest and Suppression of Activated PDGFRβ-PI3K-Akt Signaling Cascade

Cited by 21 publications

References 44 publications

Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch

Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch

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

Phenotype of Vascular Smooth Muscle Cells (VSMCs) Is Regulated by miR-29b by Targeting Sirtuin 1

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