The role of CXCR7 on the adhesion, proliferation and angiogenesis of endothelial progenitor cells
The role of CXCR7 on the adhesion, proliferation and angiogenesis of endothelial progenitor cells
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CXCR7对内皮祖细胞粘附、增殖和血管生成的作用
DOI：
10.1111/j.1582-4934.2011.01301.x
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发表时间：
2011-06-01
影响因子：
5.3
通讯作者：
Cai, Lu
中科院分区：
文献类型：
--
作者：
Dai, Xiaozhen;Tan, Yi;Cai, Lu
以往的研究证实，基质细胞衍生因子1(SDF-1)在稳态动态平衡和损伤过程中是造血干细胞和内皮祖细胞(EPC)保持、迁移和动员的主要调节因子。多年来，CXC趋化因子受体4(CXCR4)一直被认为是SDF-1的唯一受体，也是SDF-1诱导的生物学效应的唯一中介。然而，最近的研究发现，SDF-1不仅可以与CXCR4结合，还可以与CXC趋化因子受体7(CXCR7)结合。SDF-1与CXCR7结合的证据引起了人们的关注，即如何区分SDF-1/CXCR7通路和SDF-1/CXCR4通路在以前被认为是SDF-1/CXCR4的所有过程中的潜在贡献。本研究探讨了CXCR7在体外对内皮祖细胞的作用。RT-PCR、Western印迹和流式细胞仪检测表明，CXCR4和CXCR7在EPC中高表达。用其抗体或拮抗剂阻断CXCR4或CXCR7可抑制SDF-1诱导的EPC的黏附。SDF-1通过CXCR4而不是CXCR7调控内皮祖细胞的迁移。然而，阻断CXCR4或CXCR7均可抑制内皮祖细胞的跨内皮迁移。CXCR7和CXCR4在SDF-1诱导内皮祖细胞的管状形成过程中都是必不可少的。这些结果表明，CXCR7和CXCR4在内皮细胞对SDF-1的应答中都是重要的，提示CXCR7可能是血管生成依赖性疾病的另一个潜在的靶分子。
Previous studies confirmed that stromal cell-derived factor 1 (SDF-1) was a principal regulator of retention, migration and mobilization of haematopoietic stem cells and endothelial progenitor cells (EPCs) during steady-state homeostasis and injury. CXC chemokine receptor 4 (CXCR4) has been considered as the unique receptor of SDF-1 and as the only mediator of SDF-1-induced biological effects for many years. However, recent studies found that SDF-1 could bind to not only CXCR4 but also CXC chemokine receptor 7 (CXCR7). The evidence that SDF-1 binds to the CXCR7 raises a concern how to distinguish the potential contribution of the SDF-1/CXCR7 pathway from SDF-1/CXCR4 pathway in all the processes that were previously attributed to SDF-1/CXCR4. In this study, the role of CXCR7 in EPCs was investigated in vitro. RT-PCR, Western blot and flow cytometry assay demonstrate that both CXCR4 and CXCR7 were expressed highly in EPCs. The adhesion of EPCs induced by SDF-1 was inhibited by blocking either CXCR4 or CXCR7 with their antibodies or antagonists. SDF-1 regulated the migration of EPCs via CXCR4 but not CXCR7. However, the transendothelial migration of EPCs was inhibited by either blocking of CXCR4 or CXCR7. Both CXCR7 and CXCR4 are essential for the tube formation of EPCs induced by SDF-1. These results suggested that both CXCR7 and CXCR4 are important for EPCs in response to SDF-1, indicating that CXCR7 may be another potential target molecule for angiogenesis-dependent diseases.