Transforming growth factor β alters plasminogen activator activity in human skin fibroblasts

Adult human skin fibroblasts were used as a model to study the effects of transforming growth factor beta (TGFβ) on the secreted plasminogen activator (PA) activity of cultured cells. TGFβ, at nanogram concentrations, enhanced the secretion of pro-PA from two fibroblast strains in a time- and dose-dependent manner. The induced enzymatic activity was inhibited by anti-urokinase antibodies and it co-migrated with purified urokinase in polyacrylamide gels. The secretion of PA activity was abolished when cycloheximide (0.1 μg/ml) was added to the cultures. The activity was thus dependent on protein synthesis rather than just on direct activation of a plasminogen proactivator. TGFβ had only a slight mitogenic effect on the test cells. Epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and insulin were ineffective alone in inducing PA. Insulin, on the contrary, had an inhibitory effect on the TGFβ-induced PA activity. In addition to its effects on the secretion of PA, TGFβ enhanced the production of a proteinase inhibitor by these cells. The results suggest a role for TGFβ in the regulation of PA activity and pericellular proteolysis in fibroblastic cells.