Regulation of endothelial cell branching morphogenesis by endogenous chemokine stromal-derived factor-1
Regulation of endothelial cell branching morphogenesis by endogenous chemokine stromal-derived factor-1
复制标题
DOI：
10.1182/blood.v99.8.2703
复制
发表时间：
2002-04-15
期刊：
影响因子：
20.3
通讯作者：
Tosato, G
中科院分区：
文献类型：
--
作者：
Salvucci, O;Yao, L;Tosato, G
趋化因子基质衍生因子-1(SDF-1)及其独特的受体CXCR4是正常心血管发育所必需的，但SDF-1在出生后血管重塑中的关键作用以及SDF-1/CXCR-4血管生成的机制尚不清楚。在这里，我们显示SDF-1是由选定的健康和肿瘤组织的血管内皮细胞表达的。在体外，原代内皮细胞结构性地表达SDF-1，在细胞质、细胞表面和培养上清液中检测到SDF-1。血管内皮细胞生长因子和碱性成纤维细胞生长因子可促进内皮细胞SDF-1的表达。在功能研究中，百日咳毒素和SDF-1或CXCR-4抗体在体外干扰依赖细胞外基质的内皮细胞管的形成。这种形态发生过程与表面CXCR-4表达的时间依赖性调节有关，这种表达从扩散到极化，然后丢失。在体内，针对SDF-1的百日咳毒素和中和抗体抑制生长因子依赖的新生血管。这些结果表明，SDF-1/CXCR-4识别了血管内皮生长因子和碱性成纤维细胞生长因子调节的自分泌信号系统，这些信号系统是内皮细胞形态发生和血管生成的重要调节因素。(C)2002年，由美国血液病学会公布。
The chemokine stromal-derived factor-1 (SDF-1) and its unique receptor, CXCR4, are required for normal cardiovascular development, but a critical role for SDF-1 In postnatal vascular remodeling and the mechanisms underlying SDF-1/CXCR-4 vasculogenesis are unclear. Here we show that SDF-1 is expressed by the vascular endothellum from selected healthy and tumor tissues. In vitro, primary endothelial cells constitutively express SDF-1 that is detected in the cytoplasm, on the cell surface, and in the culture supernatant. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) increase SDF-1 expression In endothelial cells. In functional studies, pertussis toxin and antibodies to SDF-1 or CXCR-4 disrupt extracellular matrix-dependent endothelial cell tube formation In vitro. This morphogenic process Is associated with time-dependent modulation of surface CXCR-4 expression that changes from being diffuse to being polarized and subsequently lost. In vivo, pertussis toxin and neutralizing antibodies directed at SDF-1 inhibit growth factor-dependent neovascularization. These results indicate that SDF-1/CXCR-4 identifies VEGF and bFGF-regulated autocrine signaling systems that are essential regulators of endothelial cell morphogenesis and angiogenesis. (C) 2002 by The American Society of Hematology.