Cyclic adenosine monophosphate and protein kinase C modulate fibronectin production in cultured human mesangial cells.

To identify potential intracellular mediators of mesangial cell fibronectin production, we examined the effect of cyclic adenosine monophosphate and protein kinase C on fibronectin biosynthesis in cultured human mesangial cells. We found that increasing intracellular cyclic adenosine monophosphate resulted in a 2.6-fold increase in fibronectin mRNA expression within 15 minutes ; this reached a plateau after 1 hour and fell below control levels by 24 hours. Cyclic adenosine monophosphate significantly increased both immunoreactive fibronectin levels and the incorporation of [ 35 S]-labeled methionine into fibronectin after 1 and 2 hours (251% ± 3% and 157% ± 18% of controls, respectively). The induction of protein kinase C with phorbol ester also increased fibronectin mRNA expression. The effect was time and dose dependent. Phorbol ester significantly increased both immunoreactive fibronectin levels and the incorporation of [ 35 S]-labeled methionine after 1 and 2 hours (174% ± 2% and 224% ± 6% of controls, respectively). Inhibition of protein kinase C with calphostin C attenuated constitutive and phorbol ester induced fibronectin biosynthesis. These studies indicate that cyclic adenosine monophosphate and protein kinase C regulate mesangial cell fibronectin biosynthesis and that protein kinase C may contribute to control of constitutive fibronectin production.