Abstract
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.
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Cell Division / drug effects*
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Cells, Cultured
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DNA Replication / drug effects*
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Growth Substances / pharmacology*
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Humans
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Isoquinolines / pharmacology
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Kidney Glomerulus / cytology*
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Kidney Glomerulus / drug effects
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Kidney Glomerulus / metabolism
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Kinetics
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Pertussis Toxin
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Piperazines / pharmacology
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Plasminogen Activators / pharmacology*
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Plasminogen Inactivators / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / metabolism*
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Receptors, Urokinase Plasminogen Activator
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Tetradecanoylphorbol Acetate / pharmacology
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Thymidine / metabolism
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Urokinase-Type Plasminogen Activator / metabolism
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Urokinase-Type Plasminogen Activator / pharmacology*
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Virulence Factors, Bordetella / pharmacology
Substances
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Growth Substances
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Isoquinolines
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PLAUR protein, human
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Piperazines
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Plasminogen Inactivators
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Receptors, Cell Surface
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Receptors, Urokinase Plasminogen Activator
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Virulence Factors, Bordetella
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Pertussis Toxin
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Protein Kinase C
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Plasminogen Activators
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Urokinase-Type Plasminogen Activator
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Tetradecanoylphorbol Acetate
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Thymidine