CXCR7/CXCR4/CXCL12 轴调节脉络膜视网膜内皮细胞的增殖、迁移、存活和管形成。
CXCR7/CXCR4/CXCL12 axis regulates the proliferation, migration, survival and tube formation of choroid-retinal endothelial cells.
机构信息
Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China.
出版信息
Ophthalmic Res. 2013;50(1):6-12. doi: 10.1159/000348532. Epub 2013 Mar 21.
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.
背景/目的：基质细胞衍生因子-1（SDF-1）已被证明通过 CXCR4 介导广泛的生物学过程，CXCR4 曾被认为是其唯一的受体。CXCR7 是 SDF-1 的一个新发现的受体。本研究旨在探讨 CXCR7/CXCR4/SDF-1 轴是否参与体外缺氧模型中的脉络膜新生血管（CNV）形成。
方法
CXCR7 siRNA 和/或 CXCR4 siRNA 转染到脉络膜视网膜内皮 RF/6A 细胞系的缺氧模型中。进行 CCK-8 分析、Transwell 迁移分析、Annexin V-FITC 和碘化丙啶染色以及 Matrigel 管形成分析，以研究 CXCR4 和 CXCR7 在 SDF-1 诱导的 RF/6A 细胞增殖、迁移、存活和管形成中的作用。
结果
在缺氧条件下，CXCR4 而不是 CXCR7 介导 SDF-1 诱导的 RF/6A 细胞迁移和增殖，而 CXCR7 仅参与 RF/6A 细胞存活。此外，CXCR7 和 CXCR4 共同作用调节 RF/6A 细胞管形成。
结论
CXCR7/CXCR4/SDF-1 轴在 CNV 的形成中起重要作用，可能成为治疗与 CNV 相关疾病的新靶点。
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