Modulation of plasminogen activator inhibitor-1 and urokinase in retinal pigmented epithelial cells.
OBJECTIVE
To examine the effect of several agents that either stimulate or inhibit neovascularization on plasminogen activator inhibitor-1 and urokinase in retinal pigmented epithelial cells and vascular endothelial cells.


METHODS
Steady-state levels of messenger RNA were assessed by Northern blots and dot blots and protein levels were assessed by immunoprecipitation.


RESULTS
Data indicate that messenger RNA levels for plasminogen activator inhibitor-1 are modulated in similar fashion in both cells types, being increased by incubation with transforming growth factor-beta, dexamethasone, tumor necrosis factor, phorbol myristate acetate, and thrombin. Levels of urokinase messenger RNA in retinal pigmented epithelial cells are significantly increased only by phorbol myristate acetate and are decreased by dexamethasone and transforming growth factor-beta, whereas in endothelial cells plasminogen activator urokinase messenger RNA is increased by each of the stimuli except dexamethasone, which causes a decrease. Immunoprecipitation experiments demonstrate similar modulation of inhibitor-1 proteins secreted by retinal pigmented epithelial cells, whereas urokinase is difficult to detect.


CONCLUSIONS
These data suggest that retinal pigmented epithelial cells may help to alter proteolytic activity in the subretinal space and thereby participate, along with endothelial cells, in the regulation of choroidal neovascularization.
Wilmer Institute, Johns Hopkins Hospital, Baltimore, Maryland 21205.
S F
SF
Hackett
P A
PA
Campochiaro
D000368:Aged; D001685:Biological Factors / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007223:Infant; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D001685:Biological Factors; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D003907:Dexamethasone; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate