MicroRNA-29b inhibits migration and proliferation of vascular smooth muscle cells in neointimal formation

J Cell Biochem. 2015 Apr;116(4):598-608. doi: 10.1002/jcb.25011.

Abstract

The proliferation and migration of smooth muscle cells (SMCs) are considered to be key steps in the progression of atherosclerosis and restenosis. Certain stimuli, such as, interleukin-3 (IL-3) are known to stimulate proliferation and migration in vascular diseases. Meanwhile, microRNAs (miRs) have been revealed as critical modulators of various diseases in which miR-29b is known to regulate cell growth by targeting Mcl-1 and MMP2. However, roles of miR-29b in vascular smooth muscle cells remain almost unknown. We hypothesized that miR-29b may control the proliferation and migration processes induced by IL-3 stimulation by inhibiting its own specific targets in SMCs. MiR-29b significantly suppressed the proliferation and migration of SMCs through the inhibition of the signaling pathway related to Mcl-1 and MMP2. We also found that miR-29b expression levels significantly declined in balloon-injured rat carotid arteries and that the overexpression of miR-29b by local oligonucleotide delivery can inhibit neointimal formation. Consistent with the critical role of miR-29b in vitro, we observed down-regulated expression levels of Mcl-1 and MMP2 from the neointimal region. These results indicate that miR-29b suppressed the proliferation and migration of SMCs, possibly through the inhibition of Mcl-1 and MMP2, and suggest that miR-29b may serve as a useful therapeutic tool to treat cardiovascular diseases such as, atherosclerosis and restenosis.

Keywords: MIGRATION; MicroRNA-29b; PROLIFERATION; SMOOTH MUSCLE CELL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Artery Injuries / genetics*
  • Carotid Artery Injuries / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation
  • Interleukin-3 / pharmacology*
  • Matrix Metalloproteinase 2 / genetics
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / cytology*
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / physiology*
  • Neointima / genetics*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Interleukin-3
  • MIRN29 microRNA, rat
  • Mcl1 protein, rat
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat