CXCR7/CXCR4/CXCL12 axis regulates the proliferation, migration, survival and tube formation of choroid-retinal endothelial cells

Ophthalmic Res. 2013;50(1):6-12. doi: 10.1159/000348532. Epub 2013 Mar 21.

Abstract

Background/aims: Stromal cell-derived factor-1 (SDF-1) has been shown to mediate a broad range of biological processes via CXCR4, once regarded as its only receptor. CXCR7 is a recently identified receptor for SDF-1. This study aimed to investigate whether the CXCR7/CXCR4/SDF-1 axis is involved in choroidal neovascularization (CNV) formation in an in vitro hypoxic model.

Methods: CXCR7 siRNA and/or CXCR4 siRNA was transfected into a hypoxic model of the choroid-retinal endothelial RF/6A cell line. CCK-8 analysis, transwell migration analysis, annexin V-FITC and propidium iodide staining, and Matrigel tube formation analysis were performed to investigate the role of CXCR4 and CXCR7 in SDF-1-induced proliferation, migration, survival and tube formation of RF/6A cells.

Results: CXCR4, but not CXCR7, mediates SDF-1-induced RF/6A cell migration and proliferation under hypoxic conditions, whereas CXCR7 was exclusively involved in RF/6A cell survival. In addition, CXCR7 and CXCR4 acted together to regulate RF/6A cell tube formation.

Conclusion: The CXCR7/CXCR4/SDF-1 axis plays an important role in the formation of CNV, and may become a novel target for the treatment of CNV-associated diseases.

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Cell Movement / physiology
  • Cell Proliferation
  • Cell Survival / physiology
  • Cells, Cultured
  • Chemokine CXCL12 / physiology*
  • Choroid / cytology
  • Choroidal Neovascularization / pathology*
  • Disease Models, Animal
  • Endothelial Cells / physiology*
  • Hypoxia / metabolism
  • Macaca mulatta
  • Real-Time Polymerase Chain Reaction
  • Receptors, CXCR / physiology*
  • Receptors, CXCR4 / physiology
  • Retina / cytology

Substances

  • Chemokine CXCL12
  • Receptors, CXCR
  • Receptors, CXCR4