Petzelbauer E, Springhorn J P, Tucker A M, Madri J A
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Am J Pathol. 1996 Sep;149(3):923-31.
Vascular endothelial and smooth muscle cells exhibit reciprocal migratory responses after transforming growth factor (TGF)-beta 1 treatment. Endothelial cells exhibit a decreased migratory rate and smooth muscle cells exhibit an increased migratory rate. Previous studies have demonstrated increases in extracellular matrix and integrin synthesis and expression in response to TGF-beta 1. In this report, we illustrate the roles of plasminogen activator inhibitor in modulating the migratory rates in these two cell types. Endothelial cells appear to require a proteolytic phenotype for rapid migration, whereas vascular smooth muscle cells appear to require an anti-proteolytic phenotype. Modulation of proteinase/anti-proteinase activity ratios was accomplished via TGF-beta 1 induction, addition of exogenous plasminogen activator inhibitor, addition of anti-catalytic antibodies directed against urokinase plasminogen activator, overexpression of plasminogen activator inhibitor utilizing stable transfectants, and the use of vitronectin as a substratum. The reciprocal migratory behaviors exhibited by these two vascular cell types in response to TGF-beta 1 is discussed in the context that these two vascular cell types utilize distinct adhesive and signaling pathways in their interactions with extracellular matrix components and responsiveness to proteolytic activity.
转化生长因子（TGF）-β1处理后，血管内皮细胞和平滑肌细胞呈现出相反的迁移反应。内皮细胞迁移速率降低，而平滑肌细胞迁移速率增加。先前的研究表明，细胞外基质以及整合素的合成和表达会因TGF-β1而增加。在本报告中，我们阐述了纤溶酶原激活物抑制剂在调节这两种细胞类型迁移速率中的作用。内皮细胞似乎需要一种蛋白水解表型才能快速迁移，而血管平滑肌细胞似乎需要一种抗蛋白水解表型。通过TGF-β1诱导、添加外源性纤溶酶原激活物抑制剂、添加针对尿激酶型纤溶酶原激活物的抗催化抗体、利用稳定转染子过表达纤溶酶原激活物抑制剂以及使用玻连蛋白作为基质来调节蛋白酶/抗蛋白酶活性比率。在这两种血管细胞类型与细胞外基质成分相互作用以及对蛋白水解活性的反应中利用不同的黏附及信号通路的背景下，讨论了这两种血管细胞类型对TGF-β1呈现出的相反迁移行为。
