De Petro G, Copeta A, Barlati S
Department of Biomedical Sciences and Biotechnologies, University of Brescia, Italy.
Exp Cell Res. 1994 Jul;213(1):286-94. doi: 10.1006/excr.1994.1200.
In this study we have verified the mitogenic effect of urokinase-type (u-PA) and tissue-type plasminogen activators (t-PA) on human normal fibroblasts. We report that both PAs can induce DNA replication and cell division in serum-deprived cultured human skin fibroblasts. The activity of u-PA and t-PA is, respectively, three- and twofold more potent than that exerted by epidermal growth factor (EGF) with an activity slightly lower (50-60%) than that induced by basic fibroblast growth factor (bFGF). The u-PA and t-PA, but not plasmin, induced DNA synthesis, which could be neutralized by anti-u-PA and anti-t-PA antibodies, respectively, but was insensitive to aprotinin treatment. The addition of anti-u-PA-receptor (u-PAR) monoclonal antibodies to the assays selectively suppressed the mitogenic effect exerted by u-PA, but not that of t-PA, and the amino-terminal fragment of u-PA, containing the EGF-like domain and the kringle module, did not elicit any mitogenic activity. Anti-bFGF antibodies completely suppressed the mitogenic activity of bFGF, but did not have any effect on that of u-PA and t-PA; the activity of both PAs was inhibited by anti-fibronectin IgG concentrations ineffective on bFGF. These results indicate that PAs may be considered growth factors of human fibroblasts.
在本研究中，我们验证了尿激酶型纤溶酶原激活剂（u-PA）和组织型纤溶酶原激活剂（t-PA）对人正常成纤维细胞的促有丝分裂作用。我们报告称，两种纤溶酶原激活剂均可在血清饥饿培养的人皮肤成纤维细胞中诱导DNA复制和细胞分裂。u-PA和t-PA的活性分别比表皮生长因子（EGF）高两倍和一倍，其活性略低于碱性成纤维细胞生长因子（bFGF）诱导的活性（50-60%）。u-PA和t-PA可诱导DNA合成，但纤溶酶不能，u-PA和t-PA诱导的DNA合成可分别被抗u-PA和抗t-PA抗体中和，但对抑肽酶处理不敏感。在实验中加入抗u-PA受体（u-PAR）单克隆抗体可选择性抑制u-PA的促有丝分裂作用，但不影响t-PA的促有丝分裂作用，且含有EGF样结构域和kringle模块的u-PA氨基末端片段不具有任何促有丝分裂活性。抗bFGF抗体可完全抑制bFGF的促有丝分裂活性，但对u-PA和t-PA的促有丝分裂活性没有任何影响；两种纤溶酶原激活剂的活性均被对bFGF无效的抗纤连蛋白IgG浓度所抑制。这些结果表明，纤溶酶原激活剂可被视为人类成纤维细胞的生长因子。
