Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y, Kitamura Y, Matsushima K, Yoshida N, Nishikawa S, Kishimoto T, Nagasawa T
Department of Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Izumi, Japan.
Nature. 1998 Jun 11;393(6685):591-4. doi: 10.1038/31261.
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. 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 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. CXCR4 also functions as a co-receptor for T-cell-line tropic human immunodeficiency virus HIV-1. 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.
器官的血管化通常在其分化和生长过程中通过对预先存在的血管系统进行重塑来实现，以使它们能够在发育过程中执行其特定功能。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，已通过对突变小鼠的分析得以确定。由于这些小鼠中的大多数在许多器官发育之前就死于早期妊娠，因此尚未确定负责器官发生过程中血管化的分子。细胞表面受体CXCR4是一种七次跨膜的G蛋白偶联受体，可识别CXC趋化因子PBSF/SDF-1（前B细胞生长刺激因子/基质细胞衍生因子），该因子负责B细胞淋巴细胞生成、骨髓髓细胞生成和心室间隔形成。CXCR4还作为嗜T细胞系人类免疫缺陷病毒HIV-1的共受体发挥作用。在此我们报告，CXCR4在发育中的血管内皮细胞中表达，并且缺乏CXCR4或PBSF/SDF-1的小鼠在供应胃肠道的大血管形成方面存在缺陷。此外，缺乏CXCR4的小鼠在子宫内死亡，并且在血管发育、造血和心脏发生方面存在缺陷，这与缺乏PBSF/SDF-1的小鼠相似，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定义了一种新的器官血管化信号系统。
