MicroRNA-1 regulates the proliferation of vascular smooth muscle cells by targeting insulin-like growth factor 1

Int J Mol Med. 2015 Sep;36(3):817-24. doi: 10.3892/ijmm.2015.2277. Epub 2015 Jul 8.

Abstract

The aim of this study was to investigate the role of microRNAs (miRNAs or miRs) in vascular smooth muscle cell (VSMC) proliferation and to elucidate the underlying molecular mechanisms. In a previous study, using microarray analysis, differentially expressed miRNAs were identified in primary VSMCs isolated from the medial layer of the thoracic aorta obtained from spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats. Among others, miR-1 was identified to be downregulated in VSMCs from SHRs. Thus, in the present study, we focused on miR-1, the downregulation of which was confirmed by RT-qPCR and western blot analysis in VSMCs isolated from SHRs. We identified insulin-like growth factor 1 (IGF1) as a potential target gene of miR-1, and we subsequently validated IGF1 as a target gene of miR-1 by luciferase assay. The results revealed that the exogenous overexpression of miR-1 significantly suppressed the expression of IGF1. Additionally, we demonstrated that the downregulation of IGF1 by the introduction of miR-1 attenuated the proliferation of the VSMCs, suggesting that IGF1 is a target gene of miR-1 and that the effects of miR-1 are mediated through IGF1. In conclusion, the findings of our study demonstrate that miR-1 is significantly downregulated in VSMCs and that it is an important regulator of cell proliferation. Therefore, IGF1 may be involved in the regulation of VSMC proliferation by targeting miR-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Proliferation*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation*
  • Humans
  • Hypertension / genetics*
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Up-Regulation

Substances

  • MIRN1 microRNA, human
  • MIRN1 microRNA, rat
  • MicroRNAs
  • Insulin-Like Growth Factor I