Milan University, Department of Biomolecular Sciences and Biotechnologies, Milan, Italy.
Sci Transl Med. 2010 Nov 17;2(58):58ps53. doi: 10.1126/scitranslmed.3001793.
During development, microvessels acquire specialized functions to meet the requirements of different tissues and organs. The vasculature of the brain constitutes one of the best examples of an organ-specific and highly specialized microvasculature, in which the endothelial cells that line blood vessels form an active permeability barrier and transport system called the blood-brain barrier (BBB); little is known, however, about the molecular mechanisms that instruct endothelial cells toward a BBB phenotype. Now Kuhnert et al. reveal that the orphan heterotrimeric GTP-binding protein-coupled receptor GPR124/TEM5 acts as an organ-specific regulator of brain angiogenesis, required for normal endothelial cell sprouting, migration, and expression of the BBB marker Glut-1 in the forebrain and neural tube. These findings add to our knowledge of brain vascularization and may open up possibilities for new therapeutic regimes to treat several diseases, including stroke, brain tumors, and vascular malformations.
在发育过程中，微血管获得专门的功能以满足不同组织和器官的需求。大脑的脉管系统是具有器官特异性和高度特化的微血管的最佳范例之一，其中排列在血管中的内皮细胞形成称为血脑屏障（BBB）的主动通透性屏障和运输系统；然而，关于指导内皮细胞朝向 BBB 表型的分子机制知之甚少。现在，Kuhnert 等人揭示了孤儿异三聚体 G 蛋白偶联受体 GPR124/TEM5 作为脑血管生成的器官特异性调节剂发挥作用，对于正常的内皮细胞出芽、迁移以及在前脑和神经管中 BBB 标志物 Glut-1 的表达是必需的。这些发现增加了我们对脑血管生成的认识，并可能为治疗几种疾病（包括中风、脑肿瘤和血管畸形）的新治疗方案开辟可能性。
