MicroRNA-155 Inhibits Polarization of Macrophages to M2-Type and Suppresses Choroidal Neovascularization

Inflammation. 2018 Feb;41(1):143-153. doi: 10.1007/s10753-017-0672-8.

Abstract

Arg-1+Ym-1+ M2-type macrophages play essential roles in the development of choroidal neovascularization (CNV). Thus, inhibition of M2-type macrophages may be effective in suppressing CNV. However, the potential mechanisms of macrophage polarization during development of CNV remain unclear. In this study, we report that microRNA-155 (miR-155) inhibited M2 polarization by targeting C/EBPβ in CNV model mice and in bone marrow-derived primary macrophages. Moreover, our data show that intravitreous injection of miR-155 mimics suppressed subretinal leakage and neovascularization. Therefore, we conclude that C/EBPβ plays a significant role in M2 macrophage polarization in CNV model, while miR-155 mimics could suppress CNV by inhibiting C/EBPβ activity and M2 macrophage polarization.

Keywords: C/EBPβ; choroidal neovascularization; macrophages; miRNA-155; polarization.

MeSH terms

  • Animals
  • Arginase / genetics
  • Arginase / metabolism
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cells, Cultured
  • Choroid / metabolism*
  • Choroid / pathology
  • Choroidal Neovascularization / genetics
  • Choroidal Neovascularization / metabolism
  • Choroidal Neovascularization / pathology
  • Choroidal Neovascularization / prevention & control*
  • Dinoprostone / pharmacology
  • Disease Models, Animal
  • Laser Coagulation
  • Lectins / genetics
  • Lectins / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic*
  • Phenotype
  • Transfection
  • Vascular Endothelial Growth Factor A / metabolism
  • beta-N-Acetylhexosaminidases / genetics
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Cebpb protein, mouse
  • Lectins
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Chil3 protein, mouse
  • beta-N-Acetylhexosaminidases
  • Arg1 protein, mouse
  • Arginase
  • Dinoprostone