STIMULATION OF FIBRONECTIN SYNTHESIS THROUGH THE PROTEIN-KINASE-C SIGNALING PATHWAY IN NORMAL AND TRANSFORMED HUMAN LUNG FIBROBLASTS

We examined the role of the protein kinase C (PKC) signaling pathway i n the stimulation of fibronectin synthesis in both normal and transfor med human lung fibroblasts. Phorbol myristate acetate (PMA), a potent PKC activator, stimulated fibronectin synthesis in both normal and tra nsformed fibroblasts in a time and dose dependent fashion. Down-regula tion of PKC by prior exposure of cells to a high concentration of PMA blocked the increase in fibronectin synthesis and mRNA levels induced by PMA. Bisindolylmaleimide, a specific inhibitor of PKC, also abolish ed the PMA-induced fibronectin synthesis. 4 alpha-phorbol didecanoate, an inactive phorbol ester, failed to affect fibronectin synthesis. Th ese data suggest that PMA stimulates fibronectin synthesis and gene ex pression through the PKC signaling pathway in both normal and transfor med human lung fibroblasts.