MicroRNA-184 modulates canonical Wnt signaling through the regulation of frizzled-7 expression in the retina with ischemia-induced neovascularization

FEBS Lett. 2015 Apr 28;589(10):1143-1149. doi: 10.1016/j.febslet.2015.03.010. Epub 2015 Mar 18.

Abstract

Aberrant activation of Wnt signaling contributes to ischemia-induced retinal neovascularization in oxygen-induced retinopathy (OIR), although the underlying mechanism is so far unclear. Here, we show that microRNA-184 (miR-184) is significantly down-regulated in the retina of OIR mice, and miR-184 negatively modulates Wnt signaling both in vivo and in vitro. Furthermore, we show that the Wnt receptor, frizzled-7, is a downstream target of miR-184, and delivery of miR-184 mimic inhibits Wnt signaling in the OIR retina. These results suggest that decreased levels of miR-184 are responsible, at least in part, for the aberrant activation of Wnt signaling in ischemia-induced retinal neovascularization.

Keywords: Gene delivery; MicroRNA; Neovascularization; Oxygen-induced retinopathy; Wnt signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Frizzled Receptors
  • Ischemia / genetics
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Mice
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Retina / metabolism*
  • Retina / pathology
  • Wnt Signaling Pathway*

Substances

  • Frizzled Receptors
  • Fzd7 protein, mouse
  • MIRN184 microRNA, mouse
  • MicroRNAs
  • Receptors, G-Protein-Coupled