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 [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.
Rovin
B H
BH
Department of Internal Medicine, Ohio State University, Columbus, USA.
Tan
L C
LC
Leonhart
K L
KL
Nahman
N S
NS
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005920:Glomerular Mesangium / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D005353:Fibronectins; D009281:Naphthalenes; D010703:Phorbol Esters; D012333:RNA, Messenger; D008715:Methionine; D000242:Cyclic AMP; D011493:Protein Kinase C; C058819:calphostin C