The role of the urokinase-type plasminogen activator (uPA) and its receptor (CD87) in lipodermatosclerosis

Background: Lipodermatosclerosis refers to a sclerosing panniculitis and de rmopathy of the lower extremities sometimes seen in association with venous ulceration. Matrix metalloproteinases are implicated in the pathogenesis o f venous leg ulcers and the in vitro activation of recombinant MMP-2 is con trolled by the plasminogen activation system. To better understand the role of plasminogen activation in the pathogenesis of venous leg ulcers we inve stigated fibrinolytic factors and their inhibitors in tissue samples of lip odermatolsclerosis. Methods: The expression and the functional state of the urokinase-type plas minogen activator (uPA), the tissue-type plasminogen activator (tPA), the u rokinase receptor (CD87), the plasminogen activator inhibitors-1 and -2 (PA I-1 and PAI-2) were assayed using reverse transcription polymerase chain re action, Western blot, fibrin zymography and immunohistochemistry analyses i n 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 expressi on of uPA and CD87 could be detected. Fibrin zymography showed significantl y elevated endogenous uPA activity (p<0.01) in liposclerotic lesions compar ed to healthy controls. Conclusion: Our findings indicate that elevated plasminogen activation in l ipodermatosclerotic tissue may play a crucial role in the pathogenesis of v enous leg ulceration.