Progressive modulation of endothelial phenotype during in vitro blood vessel formation.
Progressive modulation of endothelial phenotype during in vitro blood vessel formation.
复制标题
体外血管形成过程中内皮表型的渐进调节。
DOI：
10.1016/0012-1606(91)90234-t
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发表时间：
1991
影响因子：
2.7
通讯作者：
Macarak,EJ
中科院分区：
文献类型：
--
作者：
Howard,PS;Myers,JC;Gorfien,SF;Macarak,EJ
本文以“萌芽”血管内皮细胞为体外模型，研究了与管状结构形成有关的形态学和生物合成的渐进性变化。在体外，萌芽内皮细胞自发形成，而不添加任何外源性因子，来自显示多边形/鹅卵石表型的克隆内皮细胞培养物。这些表型变异的内皮细胞分化形成相关的细胞网络或结节，并逐渐重组为管状结构。伴随着这些形态学变化，细胞外基质蛋白的生物合成被调制，通过北方印迹分析，代谢标记，和免疫细胞化学。初始发芽阶段的特征在于诱导I型胶原蛋白合成和含有ED-A结构域的纤连蛋白的出现，与它们在克隆培养物中的不存在相比，显示稳定的多边形/鹅卵石表型。组织化阶段，其中发芽的内皮细胞组装成管状结构，其特征还在于IV型胶原蛋白的表达。这些研究表明，从多边形/鹅卵石发芽文化，以及随后的管状组织的进展，涉及细胞外基质蛋白表达的重大改变。这种发育现象，虽然不完全类似于体内血管形成，但可能有助于理解基质大分子在血管生成过程中的作用。
“Sprouting” vascular endothelial cells were used as anin vitromodel system to study the progressive morphologic and biosynthetic changes associated with the formation of tubular structures.In vitro, sprouting endothelial cells formed spontaneously without the addition of any exogenous factors from cultures of cloned endothelium exhibiting a polygonal/cobblestone phenotype. These phenotypically variant endothelial cells differentiated to form associated cell networks or nodules which gradually reorganized into tubular structures. Concomitant with these morphologic changes, the biosynthesis of extracellular matrix proteins was modulated, as determined by Northern blot analysis, metabolic labeling, and immunocytochemistry. The initial sprouting phase was characterized by the induction of type I collagen synthesis and the appearance of fibronectin containing the ED-A domain, in comparison to their absence in cloned cultures displaying a stable polygonal/cobblestone phenotype. The organizational stage, where the sprouting endothelial cells assembled into tubular structures, was additionally characterized by the expression of type IV collagen. These studies demonstrate that the progression from polygonal/cobblestone to sprouting cultures, and subsequent tubular organization, involves major alterations in extracellular matrix protein expression. This developmental phenomenon, although not completely analogous to blood vessel formationin vivo, nevertheless may be helpful in understanding the role of matrix macromolecules in the angiogenic process.