title: CXCR7/CXCR4/CXCL12 axis regulates the proliferation, migration, survival and tube formation of choroid-retinal endothelial cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.forename: W-C
authors.initials: WC
authors.lastname: Zhao
authors.forename: F
authors.initials: F
authors.lastname: Yuan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D002829:Choroid / Q000166:cytology; D020256:Choroidal Neovascularization / Q000473:pathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism; D008253:Macaca mulatta; D060888:Real-Time Polymerase Chain Reaction; D054387:Receptors, CXCR / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology; D012160:Retina / Q000166:cytology
chemical_list: D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4