Docosahexaenoic acid inhibits vascular smooth muscle cell migration and proliferation by decreasing microRNA‑155 expression levels

Mol Med Rep. 2020 Oct;22(4):3396-3404. doi: 10.3892/mmr.2020.11404. Epub 2020 Aug 3.

Abstract

Vascular smooth muscle cell (VSMC) hyperplasia is a common cause of carotid restenosis. In the present study, the potential protective effects of docosahexaenoic acid (DHA) in carotid restenosis and the underlying mechanism of its effects were examined. VSMCs were treated with DHA, a polyunsaturated ω‑3 fatty acid. Cell migration and proliferation were assessed using wound healing and Cell Counting Kit‑8 assays and by measuring Ki‑67 protein levels. Additionally, the expression levels of microRNA‑155 were determined by reverse transcription‑quantitative PCR (RT‑qPCR). The involvement of microRNA‑155 in the regulation of migration and proliferation was evaluated by transfecting VSMCs with microRNA mimics and inhibitors. Moreover, the reversal of migration and proliferation after transfection of VSMCs with the microRNA mimics and subsequent treatment with DHA was investigated. A target gene of microRNA‑155 was identified using RT‑qPCR and luciferase assays. The migration and proliferation of VSMCs, as well as the expression of microRNA‑155 was inhibited by DHA stimulation. MicroRNA‑155 regulated the migration and proliferation of VSMCs. Finally, proliferation and migration of VSMCs were reduced following DHA treatment, which was mediated by an increase in the expression levels of microRNA‑155. Suppressor of cytokine signalling 1 (Socs1) was the target gene of microRNA‑155. In conclusion, DHA inhibited VSMC migration and proliferation by reducing microRNA‑155 expression. This effect may be caused by the microRNA‑155 target gene Socs1.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antagomirs / pharmacology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival
  • Cells, Cultured
  • Docosahexaenoic Acids / pharmacology*
  • Down-Regulation*
  • Gene Expression Regulation / drug effects
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling 1 Protein / genetics*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MIRN155 microRNA, rat
  • MicroRNAs
  • Socs1 protein, rat
  • Suppressor of Cytokine Signaling 1 Protein
  • Docosahexaenoic Acids