Molecular basis of endothelial cell morphogenesis in three-dimensional extracellular matrices.

摘要: Although many studies have focused on blood vessel development and new formation associated with disease processes, the question of how endothelial cells (ECs) assemble into tubes in three dimensions (i.e., EC morphogenesis) remains unanswered. morphogenesis is particularly dependent a signaling axis involving extracellular matrix (ECM), integrins, cytoskeleton, which regulates shape changes signals pathways necessary for tube formation. Recent reveal that genes regulating this matrix-integrin-cytoskeletal (MIC) are differentially expressed during morphogenesis. The Rho GTPases represent an important class molecules involved these events. Cdc42 Rac1 required process intracellular vacuole coalescence lumen three-dimensional (3D) matrices, while RhoA appears to stabilize capillary networks. Once networks established, supporting cells, such as pericytes, recruited further networks, perhaps by basement membrane assembly. Furthermore, we consider recent work showing balanced tendency newly formed regress. This morphogenesis-regression balance controlled differential gene expression VEGF, angiopoietin-2, PAI-1, well plasmin- metalloproteinase-dependent mechanism induces regression through degradation ECM scaffolds support EC-lined tubes. It our hope review will stimulate increased interest effort basic mechanisms 3D matrices.