MicroRNA-320 targeting neuropilin 1 inhibits proliferation and migration of vascular smooth muscle cells and neointimal formation

Int J Med Sci. 2019 Jan 1;16(1):106-114. doi: 10.7150/ijms.28093. eCollection 2019.

Abstract

This study shows that microRNA-320 (miR-320) is associated with many important cell functions, including cell differentiation, proliferation, migration, and apoptosis. However, the role of miR-320 in vascular smooth muscle cells (VSMCs) and proliferative vascular diseases is still completely unclear. In our study, we found that the expression of miR-320 in human VSMCs after PDGF stimulation was significantly down-regulated in time- and dose-dependent manner. Function analyses identified that miR-320 could inhibit the proliferation and migration of VSMCs in both basal and PDGF-stimulated conditions. Furthermore, Neuropilin 1 (NRP1) was demonstrated as a direct target of miR-320 in Luciferase reporter assays and miR-320 overexpression inhibited the expression of NRP1 with or without PDGF treatment. Finally, miR-320 was markedly decreased in mice carotid arteries after ligated injury, while the restoration of miR-320 via Ad-miR-320 attenuated neointimal hyperplasia by declining the NRP1 expression. The results confirmed that miR-320 regulated proliferation and migration of VSMCs and neointimal formation by targeting NRP1. These novel findings implied that the regulation of NRP1 expression by miR-320 has important significance in the early diagnosis and treatment of proliferation vascular diseases.

Keywords: miR-320; migration; neointimal formation; proliferation; vascular smooth muscle cell.

MeSH terms

  • Animals
  • Aorta / physiology
  • Carotid Arteries / physiology
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Down-Regulation
  • Humans
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / physiology*
  • Neointima / physiopathology*
  • Neuropilin-1 / metabolism*
  • Platelet-Derived Growth Factor / metabolism

Substances

  • MIRN320 microRNA, human
  • MicroRNAs
  • Platelet-Derived Growth Factor
  • Neuropilin-1