Oka Y, Hirai Y
Sumitomo Electric Industries, Yokohama, Japan.
Exp Cell Res. 1996 Jan 10;222(1):189-98. doi: 10.1006/excr.1996.0024.
Epimorphin is known as a mesenchymal factor involved in epithelial morphogenesis. This protein has, however, a curious nature in that only certain of its molecules are transported to extracellular regions after having undergone complex conformational changes. In the present study, we generated an N-terminally modified recombinant epimorphin fragment as a substitute for the extracellular epimorphin and examined n detail how this polypeptide affects cellular behavior in a model cell system. As immunohistochemical studies revealed that epimorphin is abundant in regions close to endothelial cells in venulae, we chose endothelial cells as the model cell and investigated the influence of this polypeptide on their cellular behavior in vitro. The recombinant epimorphin guided the endothelial cells to align themselves in tandem and to present a branched morphology in the three-dimensional culture system. We also discovered that the endothelial cells were induced to secrete several cytokines, including those involved in angiogenesis, and were suppressed in terms of proliferation by this molecule. These results suggest that epimorphin has a regulatory role in the activation of endothelial cells and is active in supporting the resulting cellular arrangement.
上皮形态发生素是一种参与上皮形态发生的间充质因子。然而，这种蛋白质具有一种奇特的性质，即只有其某些分子在经历复杂的构象变化后才会被转运到细胞外区域。在本研究中，我们生成了一种N端修饰的重组上皮形态发生素片段，作为细胞外上皮形态发生素的替代物，并详细研究了该多肽如何在模型细胞系统中影响细胞行为。免疫组织化学研究表明，上皮形态发生素在小静脉中靠近内皮细胞的区域丰富，因此我们选择内皮细胞作为模型细胞，并研究了该多肽对其体外细胞行为的影响。重组上皮形态发生素引导内皮细胞串联排列，并在三维培养系统中呈现分支形态。我们还发现，该分子可诱导内皮细胞分泌多种细胞因子，包括参与血管生成的细胞因子，并抑制其增殖。这些结果表明，上皮形态发生素在内皮细胞激活中具有调节作用，并在支持最终的细胞排列方面具有活性。
