TRANSFORMING GROWTH-FACTOR-BETA MODULATES PLASMINOGEN-ACTIVATOR ACTIVITY AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 EXPRESSION IN HUMAN KERATINOCYTES INVITRO

Transforming growth factor beta (TGF-β) is a multifunctional mediator with effects on cellular growth, differentiation, and extracellular matrix (ECM) metabolism. Because TGF-β stimulates fibronectin expression in cultured human keratinocytes, we wished to determine whether it might also affect ECM degradation through the plasminogen activator (PA)-plasminogen activator inhibitor (PAI) system. Immunofluorescence of human keratinocytes using a monospecific antiserum to type I PAI (PAI-1) showed enhanced cellular and ECM staining when they were cultured in the presence of TGF-β. The antiserum also identified an Mr 50,000 protein in conditioned media that was markedly enhanced by TGF-β. A corresponding stimulation of PAI-1 mRNA was demonstrated by quantitative RNA blot analysis. Total plasminogen activating activity of conditioned medium was markedly decreased by TGF-β. Zymography showed this to be at least partially due to decreased secreted urokinase activity. TGF-β may play an important role in stabilizing the provisional matrix synthesized by keratinocytes in healing wounds. © 1990.