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 in the stimulation of fibronectin synthesis in both normal and transformed human lung fibroblasts. Phorbol myristate acetate (PMA), a potent PKC activator, stimulated fibronectin synthesis in both normal and transformed fibroblasts in a time and dose dependent fashion. Down-regulation 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 abolished the PMA-induced fibronectin synthesis. 4α-phorbol didecanoate, an inactive phorbol ester, failed to affect fibronectin synthesis. These data suggest that PMA stimulates fibronectin synthesis and gene expression through the PKC signaling pathway in both normal and transformed human lung fibroblasts.