Sato Y, Okamura K, Morimoto A, Hamanaka R, Hamaguchi K, Shimada T, Ono M, Kohno K, Sakata T, Kuwano M
Department of Biochemistry, Oita Medical University, Japan.
Exp Cell Res. 1993 Feb;204(2):223-9. doi: 10.1006/excr.1993.1028.
Epidermal growth factor (EGF) stimulates the migration and proliferation of, and tissue-type plasminogen activator (tPA) synthesis in, human omental microvascular endothelial (HOME) cells in culture, as well as inducing the formation by these cells. In the present study, we examined the effects of various growth factors, i.e., transforming growth factor-alpha (TGF-alpha), insulin-like growth factor 1 (IGF-1), and hepatocyte growth factor (HGF) on HOME cells, and compared their effects with that of EGF. IGF-1 stimulated the proliferation and migration of these cells at a level comparable to EGF. EGF and TGF-alpha induced expression of tPA in HOME cells, while IGF-1 and HGF did not. EGF and TGF-alpha induced tube formation by HOME cells in type I collagen gel, while IGF-1 and HGF did not. The stimulatory effect of EGF on tube formation in the gel was blocked by anti-tPA antibody and by a serine protease inhibitor, aprotinin. When exogenous tPA and IGF-1 or HGF were added simultaneously to the culture, a marked induction of tube formation in the gel was observed. Exogenously added tPA alone, however, had no such inducible effect on tube formation. These results indicated an indispensable role of tPA in growth factor-dependent tube formation by HOME cells. Two subsets of growth factors appeared to modulate angiogenesis: One with fully active angiogenic activity which could induce PA (this included EGF and TGF-alpha), and the other, which could not induce PA and was not angiogenic, but could promote angiogenesis in the presence of PA. This subset included IGF-1 and HGF.
表皮生长因子（EGF）可刺激培养的人网膜微血管内皮（HOME）细胞的迁移、增殖以及组织型纤溶酶原激活物（tPA）的合成，并诱导这些细胞形成管状结构。在本研究中，我们检测了多种生长因子，即转化生长因子-α（TGF-α）、胰岛素样生长因子1（IGF-1）和肝细胞生长因子（HGF）对HOME细胞的影响，并将它们的作用与EGF的作用进行了比较。IGF-1刺激这些细胞增殖和迁移的程度与EGF相当。EGF和TGF-α可诱导HOME细胞中tPA的表达，而IGF-1和HGF则不能。EGF和TGF-α可诱导HOME细胞在I型胶原凝胶中形成管状结构，而IGF-1和HGF则不能。EGF对凝胶中管状结构形成的刺激作用被抗tPA抗体和丝氨酸蛋白酶抑制剂抑肽酶所阻断。当将外源性tPA与IGF-1或HGF同时加入培养物中时，可观察到凝胶中管状结构形成的明显诱导。然而，单独外源性添加tPA对管状结构形成没有这种诱导作用。这些结果表明tPA在HOME细胞依赖生长因子的管状结构形成中起不可或缺的作用。似乎有两类生长因子可调节血管生成：一类具有完全活跃的血管生成活性，可诱导PA生成（包括EGF和TGF-α）；另一类不能诱导PA生成，无血管生成活性，但在有PA存在时可促进血管生成。这类生长因子包括IGF-1和HGF。
