MiR-448 promotes vascular smooth muscle cell proliferation and migration in through directly targeting MEF2C

Environ Sci Pollut Res Int. 2017 Oct;24(28):22294-22300. doi: 10.1007/s11356-017-9771-1. Epub 2017 Aug 11.

Abstract

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a critical process in various cardiovascular diseases such as coronary artery disease (CAD), atherosclerosis, stroke, and hypertension. MicroRNAs (miRNAs) are small, short, and noncoding RNAs that inhibit gene expression through binding to the 3'-UTR (3' untranslated regions) of target gene mRNAs. We showed that the expression of miR-448 was upregulated in VSMCs from coronary atherosclerotic plaques compared with normal coronary artery tissues. We also found that PDGF-bb promoted VSMCs proliferation and could induce miR-448 expression. Ectopic miR-448 expression induced VSMCs proliferation. Overexpression of miR-448 induced ki-67 mRNA and protein expression. Moreover, we identified MEF2C was a direct target of miR-448 in VSMCs. Overexpression of miR-448 promoted VSMCs migration. Furthermore, overexpression of MEF2C decreased miR-448-induced VSMCs proliferation and migration. These evidences suggested that miR-448 played an important role in the proliferation and migration of VSMCs.

Keywords: Cardiovascular disease; Environmental science; MEF2C; Vascular smooth muscle cells; miR-448; microRNA.

MeSH terms

  • Atherosclerosis / genetics
  • Atherosclerosis / pathology*
  • Becaplermin
  • Cell Movement / drug effects
  • Cell Movement / genetics*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Humans
  • MEF2 Transcription Factors / genetics
  • MicroRNAs / genetics*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology*
  • Proto-Oncogene Proteins c-sis / pharmacology

Substances

  • MEF2 Transcription Factors
  • MEF2C protein, human
  • MIRN448 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-sis
  • Becaplermin