Cyclic adenosine monophosphate and protein kinase C modulate fibronectin production in cultured human mesangial cells
Rovin, B.H.; Tan, L.C.; Leonhart, K.L.; Nahman, N.S.
Journal of Laboratory and Clinical Medicine 126(2): 216-223
1995
ISSN/ISBN: 0022-2143 PMID: 7636394 Document Number: 446985
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 [35S]-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 [35S]-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.