Antagonistic regulation of protein kinase C-induced stimulation of fibronectin synthesis by cyclic AMP in human lung fibroblasts

We studied the interaction between cAMP and protein kinase C (PKC) signaling pathways in the regulation of fibronectin synthesis in human lung fibroblasts. Phorbol myristate acetate (PMA), a PKC activator, stimulated fibronectin synthesis and its mRNA expression in both normal and transformed human lung fibroblasts (WI-38 and WI-38 VA13, respectively). On the other hand, dibutyryl cAMP (Bt(2)cAMP), a cAMP analogue, did not alter fibronectin synthesis in both cell lines. The combined treatment of Bt(2)cAMP with PMA, however, suppressed the PMA-induced stimulation of fibronectin synthesis and mRNA expression in these cells. This study shows that cAMP pathway antagonizes PKC pathway in regulating fibronectin synthesis in human lung fibroblasts and provides an example of antagonistic interaction between cAMP and PKC signaling pathways.