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The role of the urokinase‐type plasminogen activator (uPA) and its receptor (CD87) in lipodermatosclerosis
Author(s) -
Herouy Yared,
Aizpurua Jon,
Stetter Christoph,
Dichmann Stefan,
Idzko Marco,
Hofmann Clemens,
Gitsch Gerald,
Vanscheidt Wolfgang,
Schöpf Erwin,
Norgauer Johannes
Publication year - 2001
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1034/j.1600-0560.2001.028006291.x
Subject(s) - urokinase receptor , zymography , plasminogen activator , pathogenesis , immunohistochemistry , urokinase , tissue plasminogen activator , t plasminogen activator , fibrinolysis , matrix metalloproteinase , fibrin , biology , receptor , pathology , plasminogen activator inhibitor 1 , matrilysin , immunology , endocrinology , medicine , biochemistry
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. Conclusion: Our findings indicate that elevated plasminogen activation in lipodermatosclerotic tissue may play a crucial role in the pathogenesis of venous leg ulceration.