MicroRNA-146b-3p regulates the dysfunction of vascular smooth muscle cells via repressing phosphoinositide-3 kinase catalytic subunit gamma

ABSTRACT

MicroRNAs are crucial regulators in the phenotype switch of vascular smooth muscle cells (VSMCs). Nonetheless, the role of miR-146b-3p in VSMCs remains unclear. In the present study, platelet-derived growth factor-BB (PDGF-BB) at different concentrations was employed to stimulate VSMCs for different times, to establish the model of VSMC dysfunction. The relative expression of miR-146b-3p was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of VSMCs was measured by BrdU assay. Flow cytometry analysis was employed for the analysis of cell cycle. VSMC migration was detected by Transwell assay. Phosphoinositide-3 kinase catalytic subunit-gamma (PIK3CG) and markers of VSMC differentiation, including α-SMA, SM-22α, SMMHC, and Calponin were examined employing Western blot. The targeting relationship between miR-146b-3p and PIK3CG 3ʹ-UTR was affirmed by dual-luciferase gene assay. We report that the reduction of miR-146b-3p expression was induced by PDGF-BB in a time-dependent and dose-dependent manner (P < 0.05). The overexpression of miR-146b-3p counteracted the effects of PDGF-BB on the proliferation and migration of VSMCs and increased the expressions of differentiation markers (P < 0.05). Additionally, PIK3CG expression was negatively regulated by miR-146b-3p, and the restoration of PIK3CG partly eliminated the effects of miR-146b-3p on VSMCs (P < 0.05). In summary, miR-146b-3p represses the proliferation, migration, and phenotype switch of VSMCs induced by PDGF-BB via targeting PIK3CG. Therefore, miR-146b-3p/PIK3CG may be a potential target for the treatment of atherosclerosis.

Graphical Abstract

KEYWORDS:

• Mir-146b-3p
• vascular smooth muscle cells
• phosphoinositide-3 kinase catalytic subunit-gamma
• platelet-derived growth factor-bb

Highlight

1. MiR-146b-3p expression is down-regulated in VSMCs after the treatment of PDGF-BB.

2. MiR-146b-3p inhibits the proliferation and migration of VSMCs and modulates the phenotype switch of VSMCs.

3. The regulatory effects of miR-146b-3p on VSMCs are partly dependent on PIK3CG, and miR-146-3p and PIK3CG are promising targets for the treatment of atherosclerosis.

Acknowledgements

We thank Hubei Yican Health Industry Co., Ltd. for its linguistic assistance during the preparation of this manuscript.

Disclosure of potential conflicts of interest

No potential conflict of interest was reported by the author(s).

Ethics statement

The ethics statement is not required since the study includes no experiments involving animal or human tissues.

Authors’ contribution

YG, XJZ, and FG designed the research project and experiments;

XJZ, LS, and WL performed dataset analysis, cell culture, and qRT-PCR;

XJZ, WL, WW, and XZH conducted the rest of the experiments;

XZH performed the statistical analysis.

All authors participated in the paper writing. All authors read and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The authors have no funding to report.