Transforming growth factor beta 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 (TGF beta) on the secreted plasminogen activator (PA) activity of cultured cells. TGF beta, 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 microgram/ml) was added to the cultures. The activity was thus dependent on protein synthesis rather than just on direct activation of a plasminogen proactivator. TGF beta 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 TGF beta-induced PA activity. In addition to its effects on the secretion of PA, TGF beta enhanced the production of a proteinase inhibitor by these cells. The results suggest a role for TGF beta in the regulation of PA activity and pericellular proteolysis in fibroblastic cells.
D000906:Antibodies; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000096:biosynthesis* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012867:Skin; D015291:Transforming Growth Factors; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology
D000906:Antibodies; D007328:Insulin; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003513:Cycloheximide; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator