Zhang J, Hughes Se
Department of Pathology, Royal Free and University College Medical School, London, WC1E 6JJ, UK.
J Pathol. 2006 Mar;208(4):453-61. doi: 10.1002/path.1937.
Angiogenesis is a highly complex orchestrated process that plays a critical role in normal development and in the pathophysiology of multiple disease processes, including tumour neovascularization, ischaemic recovery, and wound healing. In recent years there has been a resurgence of interest in Eph receptors and their ligands, ephrins, as their participation in vasculogenesis and angiogenesis has become apparent. The Eph receptor family is the largest family of receptor tyrosine kinases identified to date. The Eph receptors and their membrane-anchored ligands, ephrins, are unique in that they mediate bi-directional signalling. This is concomitant with activation of the Eph receptor tyrosine kinase domain and transduction of the typical forward signal into the receptor-bearing cell. The ligand-receptor interaction also leads to transduction of a reverse signal into the ephrin-bearing cell. The Eph/ephrin signalling mechanism is responsible for diverse and complex biological functions mediated by Eph receptors and ephrin ligands. These include vascular development, tissue-border formation, cell migration, axon guidance, and synaptic plasticity. The role of Eph receptors and ephrins in the processes of development of the cardiovascular system, angiogenesis, and vascular remodelling has been the subject of intense investigation since they were first identified in 1987. This review addresses the role of this new growth factor receptor tyrosine kinase family in those processes and provides new insights into the way in which Eph receptors and ephrin ligands modulate the angiogenic response and participate in vascular remodelling and vascular boundary formation during development of the cardiovascular system and vascularization of cancer.
血管生成是一个高度复杂的协调过程，在正常发育以及多种疾病过程的病理生理学中发挥着关键作用，这些疾病过程包括肿瘤新生血管形成、缺血恢复和伤口愈合。近年来，人们对Eph受体及其配体（ephrins）的兴趣再度兴起，因为它们在血管生成和血管生成中的参与已变得明显。Eph受体家族是迄今为止鉴定出的最大的受体酪氨酸激酶家族。Eph受体及其膜锚定配体ephrins的独特之处在于它们介导双向信号传导。这伴随着Eph受体酪氨酸激酶结构域的激活以及典型正向信号向受体细胞的转导。配体 - 受体相互作用还导致反向信号转导到携带ephrin的细胞中。Eph/ephrin信号传导机制负责由Eph受体和ephrin配体介导的多样而复杂的生物学功能。这些功能包括血管发育、组织边界形成、细胞迁移、轴突导向和突触可塑性。自1987年首次被发现以来，Eph受体和ephrins在心血管系统发育、血管生成和血管重塑过程中的作用一直是深入研究的主题。本综述探讨了这个新的生长因子受体酪氨酸激酶家族在这些过程中的作用，并为Eph受体和ephrin配体在心血管系统发育和癌症血管生成过程中调节血管生成反应、参与血管重塑和血管边界形成的方式提供了新的见解。
