Jimi S, Ito K, Kohno K, Ono M, Kuwano M, Itagaki Y, Ishikawa H
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan.
Biochem Biophys Res Commun. 1995 Jun 15;211(2):476-83. doi: 10.1006/bbrc.1995.1838.
Angiogenin is a potent angiogenic molecule in the chick chorioallantoic membrane assay and rabbit corneal assay. However, no angiogenic activity has been reported in in vitro system. In this study, we isolated and purified angiogenin from bovine milk, and the biological effect of the bovine angiogenin on bovine endothelial cells was examined in in vitro angiogenesis models. Bovine angiogenin significantly stimulated both cell migration and formation of tube-like structures in the collagen gel by bovine aortic endothelial cells. Angiogenin at 10-100 ng/ml stimulated about 2-fold higher the tube formation when basic fibroblast growth factor (bFGF) at 10 ng/ml stimulated about 3-fold over the control. Tubular morphogenesis stimulated by bFGF or angiogenin was almost completely blocked in the presence of aprotinin, an inhibitor of serine proteases. Angiogenin up-regulated both mRNA level and activity of urokinase type plasminogen activator, a key mediator of angiogenesis. Moreover, both bFGF and bovine angiogenin induced a marked increase of c-fos mRNA level at 30 min after stimulation. These novel effects of bovine angiogenin are to be discussed in relation to its structure specificity.
血管生成素在鸡胚绒毛尿囊膜试验和兔角膜试验中是一种有效的血管生成分子。然而，在体外系统中尚未报道其血管生成活性。在本研究中，我们从牛乳中分离并纯化了血管生成素，并在体外血管生成模型中检测了牛血管生成素对牛内皮细胞的生物学效应。牛血管生成素显著刺激了牛主动脉内皮细胞在胶原凝胶中的细胞迁移和管状结构的形成。当10 ng/ml的碱性成纤维细胞生长因子（bFGF）刺激形成的管状结构比对照高约3倍时，10 - 100 ng/ml的血管生成素刺激形成的管状结构约高2倍。在丝氨酸蛋白酶抑制剂抑肽酶存在的情况下，bFGF或血管生成素刺激的管状形态发生几乎完全被阻断。血管生成素上调了尿激酶型纤溶酶原激活剂的mRNA水平和活性，尿激酶型纤溶酶原激活剂是血管生成的关键介质。此外，bFGF和牛血管生成素在刺激后30分钟均诱导c-fos mRNA水平显著升高。将结合牛血管生成素的结构特异性对这些新发现的效应进行讨论。
