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PDGF-BB promotes vascular smooth muscle cell migration by enhancing Pim-1 expression via inhibiting miR-214.


ABSTRACT:

Background

Several studies have indicated that the platelet-derived growth factor/platelet-derived growth factor receptor (PDGF/PDGFR) pathway is involved in the process of atherosclerosis. However, its underlying mechanism remains to be further elucidated. Serine/threonine-protein kinase pim-1 (Pim-1), a member of serine/threonine-specific kinases, is a pro-oncogene published to be related to cell proliferation, apoptosis, and metastasis of cancer cells. Whether Pim-1 is involved in PDGF/PDGFR pathway-mediated coronary atherosclerotic heart disease remains to be elucidated.

Methods

We established a cell model of PDGF-BB-stimulated smooth muscle cells using A7r5 cells. Transwell assay was used to detect the potential of cell migration and invasion. The targeted regulation of Pim-1 by miR-214 was confirmed by luciferase assay. Rescue experiments were performed to determine the role of the PDGF-BB/miR-214/Pim-1 axis on the cell migration of smooth muscle cells by including PDGF-BB treatment, and the overexpression of miR-214 and Pim-1. Quantitative polymerase chain reaction (qPCR) was used to examine the gene expression and western blot was performed to detect the protein expression.

Results

Our data indicated that PDGF-BB could effectively enhance smooth muscle cell migration. We also showed Pim-1 was a target of miR-214 in A7r5 cells. The expression of Pim-1 was shown to be upregulated by PDGF-BB via suppression of the expression of miR-214. Moreover, overexpression miR-214 inhibited PDGF-BB-stimulated Pim-1 expression and smooth muscle cell migration via modulating epithelial-mesenchymal transition (EMT), but no change on cell cycle. However, overexpression of Pim-1 reversed miR-214-blocked cell migration by promoting the activation of the STAT3, AKT, and ERK signaling pathways.

Conclusions

Our data suggested that the PDGF/miR-214/Pim-1 axis could be a potential target for coronary atherosclerotic heart disease.

SUBMITTER: Zhou J 

PROVIDER: S-EPMC8743727 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

PDGF-BB promotes vascular smooth muscle cell migration by enhancing Pim-1 expression via inhibiting miR-214.

Zhou Jinshan J   Shao Lifang L   Yu Jianghao J   Huang Junchao J   Feng Qiang Q  

Annals of translational medicine 20211201 23


<h4>Background</h4>Several studies have indicated that the platelet-derived growth factor/platelet-derived growth factor receptor (PDGF/PDGFR) pathway is involved in the process of atherosclerosis. However, its underlying mechanism remains to be further elucidated. Serine/threonine-protein kinase pim-1 (Pim-1), a member of serine/threonine-specific kinases, is a pro-oncogene published to be related to cell proliferation, apoptosis, and metastasis of cancer cells. Whether Pim-1 is involved in PDG  ...[more]

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