Dexamethasone coordinately inhibits plasminogen activator gene expression and enzyme activity in porcine kidney cells

The peptide hormone, calcitonin, induces urokinase-type plasminogen activator (uPA) enzyme activity in cultured LLC-PK1 pig kidney cells. This induction occurs as a consequence of transcriptional activation of the uPA gene. Treatment with the synthetic glucocorticoid hormone, dexamethasone, was found to inhibit calcitonin induction of uPA enzyme activity by as much as 80%. The inhibitory effect of dexamethasone was attributed to at least two mechanisms: induction of an inhibitor of uPA enzyme activity, and reduction in uPA mRNA levels. Study on reduction of uPA mRNA levels showed that dexamethasone significantly reduced the transcription rate of the calcitonin-induced uPA gene, without affecting the half-life of uPA mRNA. Although dexamethasone has been reported to induce inhibitors of plasminogen activator enzyme activity and to inhibit transcription of various genes, the system described here appears novel in that both actions are coordinated.