Growth factor-like effect of urokinase type plasminogen activator in human renal cells.
Human renal glomerular epithelial cells possess membrane urokinase receptors. Addition of purified active urokinase to these cells in serum free minimum medium induced a dose-dependent increase in 3H-thymidine incorporation and a doubling of cell number after 48 hours of incubation. Both receptor occupancy and enzymatic activity of u-PA were required to stimulate cell proliferation. This effect was inhibited by down regulation of protein kinase C (PKC) or by H7, an inhibitor of PKC. It involved a pertussis toxin-sensitive pathway. This effect of urokinase was additive with EGF but not with thrombin growth factor activity and was not inhibited by aprotinin, an inhibitor of plasmin.
He
C J
CJ
INSERM U 64, Hôpital Tenon, Paris, France.
Rebibou
J M
JM
Peraldi
M N
MN
Meulders
Q
Q
Rondeau
E
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D010960:Plasminogen Activators / Q000494:pharmacology*; D015849:Plasminogen Inactivators / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D006133:Growth Substances; D007546:Isoquinolines; C524898:PLAUR protein, human; D010879:Piperazines; D015849:Plasminogen Inactivators; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010566:Virulence Factors, Bordetella; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine