The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract
The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract
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DOI：
10.1038/31261
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发表时间：
1998-06-11
期刊：
影响因子：
64.8
通讯作者：
Nagasawa, T
中科院分区：
文献类型：
--
作者：
Tachibana, K;Hirota, S;Nagasawa, T
器官的血管化通常发生在其分化和生长过程中对原有血管系统的重塑，使其能够在发育过程中发挥其特定的功能。早期血管系统所需的分子，其中许多是受体酪氨酸激酶及其配体，已经通过对突变小鼠的分析确定（1-3）。由于大多数小鼠在妊娠早期死亡，许多器官尚未发育成熟，因此在器官发生过程中负责血管形成的分子尚未确定。细胞表面受体CXCR4（文献4-6）是CXC趋化因子PBSF/SDF-1 （b细胞前生长刺激因子/基质细胞衍生因子）的7跨膜g蛋白偶联受体，它负责b细胞淋巴生成、骨髓生成和心脏室间隔形成(7)。CXCR4也可作为t细胞系嗜性人类免疫缺陷病毒HIV-1的共受体（文献8）。在这里，我们报道了CXCR4在发育中的血管内皮细胞中表达，并且缺乏CXCR4或PBSF/SDF-1的小鼠存在供应胃肠道的大血管形成缺陷。此外，与缺乏PBSF/SDF-1的小鼠一样，缺乏CXCR4的小鼠在子宫内死亡，在血管发育、造血和心脏发生方面存在缺陷，这表明CXCR4是PBSF/SDF-1的主要生理受体。我们得出结论，PBSF/SDF-1和CXCR4定义了一个新的器官血管化信号系统。
Vascularization of organs generally occurs by remodelling of the preexisting vascular system during their differentiation and growth to enable them to perform their specific functions during development. The molecules required by early vascular systems, many of which are receptor tyrosine kinases and their ligands, have been defined by analysis of mutant mice(1-3). As most of these mice die during early gestation before many of their organs have developed, the molecules responsible for vascularization during organogenesis have not been identified. The cell-surface receptor CXCR4 (refs 4-6) is a seven-transmembrane-spanning, G-protein-coupled receptor for the CXC chemokine PBSF/SDF-1 (for pre-B-cell growth-stimulating factor/stromal-cell-derived factor), which is responsible for B-cell lymphopoiesis, bone-marrow myelopoiesis and cardiac ventricular septum formation(7). CXCR4 also functions as a co-receptor for T-cell-line tropic human immunodeficiency virus HIV-1 (ref. 8). Here we report that CXCR4 is expressed in developing vascular endothelial cells, and that mice lacking CXCR4 or PBSF/SDF-1 have defective formation of the large vessels supplying the gastrointestinal tract. In addition, mice lacking CXCR4 die in utero and are defective in vascular development, haematopoiesis and cardiogenesis, like mice lacking PBSF/SDF-1, indicating that CXCR4 is a primary physiological receptor for PBSF/SDF-1. We conclude that PBSF/SDF-1 and CXCR4 define a new signalling system for organ vascularization.