The role of the urokinase-type plasminogen activator (uPA) and its receptor (CD87) in lipodermatosclerosis.
BACKGROUND
Lipodermatosclerosis refers to a sclerosing panniculitis and dermopathy of the lower extremities sometimes seen in association with venous ulceration. Matrix metalloproteinases are implicated in the pathogenesis of venous leg ulcers and the in vitro activation of recombinant MMP-2 is controlled by the plasminogen activation system. To better understand the role of plasminogen activation in the pathogenesis of venous leg ulcers we investigated fibrinolytic factors and their inhibitors in tissue samples of lipodermatolsclerosis.


METHODS
The expression and the functional state of the urokinase-type plasminogen activator (uPA), the tissue-type plasminogen activator (tPA), the urokinase receptor (CD87), the plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) were assayed using reverse transcription polymerase chain reaction, Western blot, fibrin zymography and immunohistochemistry analyses in tissue samples of lipodermatosclerosis.


RESULTS
Our results provide direct evidence of elevated expression of uPA (p<0.01) and CD87 (p<0.01) mRNA and protein level in lipodermatosclerosis in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and CD87 could be detected. Fibrin zymography showed significantly elevated endogenous uPA activity (p<0.01) in liposclerotic lesions compared to healthy controls.


CONCLUSIONS
Our findings indicate that elevated plasminogen activation in lipodermatosclerotic tissue may play a crucial role in the pathogenesis of venous leg ulceration.
Herouy
Y
Y
Department of Dermatology, University Medical Center, Freiburg, Germany. herouy@haut.ukl.uni-freiburg.de
Aizpurua
J
J
Stetter
C
C
Dichmann
S
S
Idzko
M
M
Hofmann
C
C
Gitsch
G
G
Vanscheidt
W
W
Schöpf
E
E
Norgauer
J
J
D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012594:Scleroderma, Localized / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; 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; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator