miR-599 Inhibits Vascular Smooth Muscle Cells Proliferation and Migration by Targeting TGFB2

PLoS One. 2015 Nov 9;10(11):e0141512. doi: 10.1371/journal.pone.0141512. eCollection 2015.

Abstract

Aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of cardiovascular diseases including coronary heart disease, restenosis and atherosclerosis. MicroRNAs are a class of small, non-coding and endogenous RNAs that play critical roles in VSMCs function. In this study, we showed that PDGF-bb, as a stimulant, promoted VSMCs proliferation and suppressed the expression of miR-599. Moreover, overexpression of miR-599 inhibited VSMCs proliferation and also suppressed the PCNA and ki-67 expression. In addition, we demonstrated that ectopic expression of miR-599 repressed the VSMCs migration. We also showed that miR-599 inhibited type I collagen, type V collagen and proteoglycan expression. Furthermore, we identified TGFb2 as a direct target gene of miR-599 in VSMCs. Overexpression of TGFb2 reversed miR-599-induced inhibition of VSMCs proliferation and type I collagen, type V collagen and proteoglycan expression. In conclusion, our findings suggest miR-599 plays a crucial role in controlling VSMCs proliferation and matrix gene expression by regulating TGFb2 expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Becaplermin
  • Cell Line
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Collagen Type I / biosynthesis
  • Collagen Type V / biosynthesis
  • Coronary Disease / genetics
  • Coronary Disease / pathology
  • Coronary Restenosis / genetics
  • Coronary Restenosis / pathology
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Muscle, Smooth, Vascular / cytology*
  • Proteoglycans / biosynthesis
  • Proto-Oncogene Proteins c-sis / metabolism*
  • Transforming Growth Factor beta2 / biosynthesis
  • Transforming Growth Factor beta2 / genetics*

Substances

  • Collagen Type I
  • Collagen Type V
  • MIRN599 microRNA, human
  • MicroRNAs
  • Proteoglycans
  • Proto-Oncogene Proteins c-sis
  • TGFB2 protein, human
  • Transforming Growth Factor beta2
  • Becaplermin

Grants and funding

This research was funded by a grant from the Science and Technology Research Project of Department of Education of Heilongjiang Province (12541434), Heilongjiang Provincial Science and Technology Research Project (LC2012C03), National Science Foundation of China (81471805), Chinese Postdoctoral Science Foundation (2014 M551272), and Scienctific Research Project of Educational Department of Heilongjiang Province (11531109) to KK. URL is http://www.nsfc.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.