G. Depetro et al., UROKINASE-TYPE AND TISSUE-TYPE PLASMINOGEN ACTIVATORS AS GROWTH-FACTORS OF HUMAN FIBROBLASTS, Experimental cell research, 213(1), 1994, pp. 286-294
In this study we have verified the mitogenic effect of urokinase-type
(u-PA) and tissue-type plasminogen activators (t-PA) on human normal f
ibroblasts. We report that both PAs can induce DNA replication and cel
l division in serum-deprived cultured human skin fibroblasts. The acti
vity of u-PA and t-PA is, respectively, three- and twofold more potent
than that exerted by epidermal growth factor (EGF) with an activity s
lightly lower (50-60%) than that induced by basic fibroblast growth fa
ctor (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, re
spectively, but was insensitive to aprotinin treatment. The addition o
f anti-u-PA-receptor (u-PAR) monoclonal antibodies to the assays selec
tively suppressed the mitogenic effect exerted by u-PA, but not that o
f t-PA, and the amino-terminal fragment of u-PA, containing the EGF-li
ke domain and the kringle module, did not elicit any mitogenic activit
y. Anti-bFGF antibodies completely suppressed the mitogenic activity o
f bFGF, but did not have any effect on that of u-PA and t-PA; the acti
vity 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. (C) 1994 Academic Press, Inc.