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

Bioengineered. 2021 Dec;12(1):2627-2638. doi: 10.1080/21655979.2021.1937904.

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 3'-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.

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

MeSH terms

  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Base Sequence
  • Becaplermin / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Class Ib Phosphatidylinositol 3-Kinase / metabolism*
  • Down-Regulation / drug effects
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology*
  • Phenotype

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • Becaplermin
  • Class Ib Phosphatidylinositol 3-Kinase
  • PIK3CG protein, human

Grants and funding

The authors have no funding to report.