Regulation of the expression of type 1 plasminogen activator inhibitor in Hep G2 cells by epidermal growth factor.
To identify factors potentially influencing expression of type 1 plasminogen activator inhibitor (PAI-1), we characterized the human tissue-specific distribution of PAI-1 mRNA and the influence of epidermal growth factor (EGF) on expression of steady state levels of PAI-1 mRNA and secretion of PAI-1 by Hep G2 cells. Two species of PAI-1 mRNA (3.2 and 2.2 kilobases) were detected, and the ratio of the two varied among tissues (3 to 5:1) in contrast to the 1:1 ratio detected in Hep G2 cells. Expression of PAI-1 mRNA was inversely related to the distribution of tissue-type plasminogen activator mRNA (2.3 kilobases). Nu-Serum, a growth media supplement, increased steady state levels of PAI-1 mRNA 5-fold within 3 h. Factors responsible were found to be trypsin-sensitive and dialysis-resistant. Antisera to EGF attenuated Nu-Serum-induced increases of PAI-1 mRNA by 57%, suggesting that EGF or EGF homologous peptides contributed to the response. EGF elicited increases of PAI-1 mRNA levels in a dose-dependent manner. Induction was rapid (7-fold at 3 h with 5 ng/ml) and complete within 10 h. The response was not attenuated by cycloheximide (25 micrograms/ml). Factor X and glyceraldehyde-3-phosphate dehydrogenase mRNA did not increase. Increased levels of PAI-1 antigen were detected in conditioned media of Hep G2 cells by 4 h and were maximal at 8 h (6-fold). We conclude that the expression of PAI-1 mRNA is tissue-specific and regulated by epidermal growth factor in Hep G2 cells.
Lucore
C L
CL
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Fujii
S
S
Wun
T C
TC
Sobel
B E
BE
Billadello
J J
JJ
D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005170:Factor X / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D009928:Organ Specificity; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D005170:Factor X; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010960:Plasminogen Activators