Distinct patterns of microvascular endothelial cell morphology are determined by extracellular matrix composition
Distinct patterns of microvascular endothelial cell morphology are determined by extracellular matrix composition
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DOI：
10.1080/10623320490512093
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发表时间：
2004-05-01
影响因子：
--
通讯作者：
Clark, P
中科院分区：
文献类型：
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作者：
Dye, JF;Lawrence, L;Clark, P
内皮与细胞外基质 (ECM) 的相互作用在血管生成中发挥重要作用，但特定的 ECM 信号是否可以确定特定的细胞形态尚不清楚。作者比较了表型不同的人胎盘微血管内皮细胞 (HPMEC) 与大血管内皮细胞 (HUVEC) 的体外 ECM 诱导的形态学反应。 HPMEC 对 I 型胶原蛋白或 IV 型胶原蛋白（单层破坏、发芽、迁移）和基质胶或层粘连蛋白 A（肠套叠、索状形成、肾小管形成）表现出不同的重组模式，并对纤维蛋白表现出中间反应；而 HUVEC 对胶原蛋白 1 和基质胶的反应类似（伸长、晶格形成、空泡化），对纤维蛋白几乎没有反应。尽管血清、酸性或碱性成纤维细胞生长因子（aFGF、bFGF）或血管内皮生长因子（VEGF）可增加 HPMEC 的胶原蛋白和基质胶反应程度，并且随基质蛋白浓度而变化，但基本模式是基质特异性的，并且与纤连蛋白无关。胶原反应与粘附和紧密连接的破坏以及丝状突起的形成相关。基质胶反应与 VE-钙粘蛋白连接定位的上调有关，而肾小管发生主要通过细胞旁重塑而不是细胞内空泡形成。总的来说，这些发现表明不同的 ECM 相互作用会刺激特定的形态反应。这些信号可能调节血管生成周期中的形态行为，使内皮细胞在迁移和血管生成表型之间切换。
Endothelial interactions with the extracellular matrix (ECM) play important roles in angiogenesis but whether specific ECM signals can determine specific cellular morphologies is unclear. The authors compared in vitro ECM-induced morphological responses of the phenotypically distinct human placental microvascular endothelial cells (HPMECs) with large vessel endothelial cells (HUVECs). HPMECs showed distinct patterns of reorganization in response to collagen-I or coliagen-IV (monolayer disruption, sprouting, migration) and Matrigel or laminin-A (intussusception, cord formation, tubulogenesis), and an intermediate response to fibrin; whereas HUVECs responded similarly to collagen-1 and Matrigel (elongation, lattice formation, vacuolation) and showed little response to fibrin. Although the extent of collagen and Matrigel responses of HPMECs were increased by serum, acidic or basic fibroblast growth factor (aFGF, bFGF), or vascular endothelial growth factor (VEGF), and varied with matrix protein concentration, the basic patterns were matrix specific, and were independent of fibronectin. The collagen responses correlated with disruption of adherens and tight junctions and the formation of filopodial protrusions. Matrigel responses were associated with up-regulated junctional localization of VE-cadherin, and tubulogenesis developed mainly through paracellular remodeling rather than intracellular vacuolation. Overall, these findings suggest that distinct ECM interactions stimulate specific morphological responses. These signals may regulate morphological behaviour in the angiogenesis cycle, switching endothelial cells between migratory and vasculogenic phenotypes.