J Jin1, W-C Zhao, F Yuan. 1. Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China.
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.
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.
Authors: M J Walters; K Ebsworth; R D Berahovich; M E T Penfold; S-C Liu; R Al Omran; M Kioi; S B Chernikova; D Tseng; E E Mulkearns-Hubert; M Sinyuk; R M Ransohoff; J D Lathia; J Karamchandani; H E K Kohrt; P Zhang; J P Powers; J C Jaen; T J Schall; M Merchant; L Recht; J M Brown Journal: Br J Cancer Date: 2014-01-14 Impact factor: 7.640