Plasminogen activation in venous leg ulcers.
BACKGROUND
Venous leg ulceration results from chronic venous insufficiency of the lower extremities. We recently showed that matrix metalloproteinase (MMP) -2 plays a major part in the pathogenesis of venous leg ulcers. In vitro activation of recombinant MMP-2 is controlled by the activity of the urokinase-type plasminogen activator (uPA), which acts as a fibrin-independent plasminogen activator. The activity of MMP-2 is potentiated by binding of uPA to the uPA receptor (uPAR).


OBJECTIVE
We aimed to clarify the role of plasminogen activation in venous leg ulcers.


METHODS
The expression of uPA, uPAR, the tissue-type plasminogen activator, and plasminogen activator inhibitor (PAI) -1 and PAI-2 was investigated using reverse transcription followed by polymerase chain reaction and Western blotting.


RESULTS
These provided direct evidence of elevated expression of uPA and uPAR at the mRNA and protein levels in venous leg ulcers, in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and uPAR was detected. Fibrin zymography showed significantly elevated endogenous uPA activity in venous leg ulcers in comparison with healthy controls.


CONCLUSIONS
Our findings indicate venous leg ulcers to be characterized by elevated plasminogen activation, suggesting that this enzyme cascade plays a crucial part in maintaining proteolytic activity in venous leg ulcers.
Herouy
Y
Y
Department of Dermatology, University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. herouy@haut.ukl.uni-freiburg.de
Trefzer
D
D
Hellstern
M O
MO
Stark
G B
GB
Vanscheidt
W
W
Schöpf
E
E
Norgauer
J
J
D000368:Aged; D002196:Capillaries / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism; D010960:Plasminogen Activators / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014647:Varicose Ulcer / Q000201:enzymology / Q000503:physiopathology*
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator