Soluble urokinase plasminogen activator receptor in venous ulcers

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

Name dc:type.qualificationname

Doctor of Medicine by Research

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2014

Author dc:creator

• Ahmad, Anwar

Advisors dc:contributor.advisor

• Burnand, Kevin Guiver
• Smith, Alberto

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/74f5dffc-db59-478e-bf87-46b476092e31

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/74f5dffc-db59-478e-bf87-46b476092e31