MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain

Gene Ther. 2014 Jan;21(1):37-43. doi: 10.1038/gt.2013.55. Epub 2013 Oct 24.

Abstract

Angiogenesis and neurogenesis are crucial processes for brain tissue repair and remodeling after brain injury. Current study shows that microRNA-210 (miR-210) promotes vascular endothelial cell migration and tube formation under hypoxia in vitro. Whether miR-210 overexpression promotes focal angiogenesis and neurogenesis in the normal adult brain is unknown. Adult male C57BL/6 mice (n=54) underwent stereotactic injection of a lentiviral vector carrying miR-210 (LV-miR-210). Following 28 days of miR-210 gene transfer, endothelial cell and neural precursor cell proliferation, microvessel density and downstream angiogenic factor were genotyped. miR-210 was highly expressed in neurons, astrocytes and endothelial cells of the LV-miR-210-injected brain hemisphere. The endothelial cell proliferation and the number of newly formed microvessels were greatly increased in the LV-miR-210-treated mice compared with the controls (P<0.05). Neural progenitor cells in the subventricular zone were greatly increased compared with the controls (P<0.05). The data indicate that miR-210 is a key factor at the microRNA level in promoting angiogenesis and neurogenesis, which was associated with local increased vascular endothelial growth factor (VEGF) levels, suggesting that miR-210 may be a potential target for ischemic stroke therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Brain / blood supply
  • Brain / physiology*
  • Endothelial Cells / metabolism
  • Genetic Vectors*
  • Lentivirus / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Microvessels / metabolism
  • Neovascularization, Physiologic*
  • Neurogenesis*
  • Neurons / metabolism
  • Transduction, Genetic
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • MIRN210 microRNA, mouse
  • MicroRNAs
  • Vascular Endothelial Growth Factor A