Soluble urokinase plasminogen activator receptor in venous ulcers

• Main Author: Ahmad, Anwar
• Published: King's College London (University of London) 2014
• Subjects: 616.5
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.628456

Compression therapy remains the only treatment option for venous ulcers with <100% success. A better understanding of the mechanisms regulating venous ulcer healing might give rise to better treatments. Urokinsae plasminogen activator receptor (uPAR), a GPI anchored 3‐domain protein exists either attached to cell wall or in soluble forms (suPARI‐III, suPARI & suPARII‐III fragments). Cleavage of uPAR results in a number of nonproteolytic functions that may be important in wound healing. Our aim was to determine whether suPAR and its fragments are present in the environment of venous ulcers and whether this receptor has a role in ulcer‐healing. Ulcer exudates and ulcer tissue biopsies were obtained from patients with confirmed venous leg ulcers. Venous ulcers that healed within 6months of compression therapy were classified as healers (H) while those that did not heal in this time were defined as non‐healers (NH). Time resolved fluorescence immunoassays (TR‐FIA) were validated for measurement of suPAR fragments. TR‐FIAs specifically detected their antigens in wound exudates, but not in tissue homogenates. All forms of suPAR fragments were detected within venous ulcer exudates. Levels of all 3 suPAR fragments were significantly higher in exudates obtained from H compared to NH. ELISA analysis of uPA and plasminogen acitvator inhibitor (PAI‐1) antigen revealed that levels were similar in ulcer exudates and tissue homogenates from H and NH. 9 Treatment of scratched keratinocyte cultures with exudates from H resulted in a greater coverage of the scratch compared with NH. Depletion of suPAR from exudates obtained from H resulted in cell death. Results from this study have shown the presence of suPAR fragments within venous ulcers with higher presence of suPAR fragments in H compared to NH. This data suggests a role of suPAR and its fragments in ulcer healing, although the precise mechanisms involved remain to be identified. Measurement of suPAR fragments may provide a prognostic indicator and a therapeutic target for the treatment of venous ulcers.