title: The soluble urokinase plasminogen activator receptor and its fragments in venous ulcers.
abstract: OBJECTIVE
  Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic functions that include chemotaxis, adhesion, and proliferation, which also have a role in wound healing. The aim of this study was to determine whether suPAR and its cleaved fragments are present in venous ulcers and whether their levels are associated with healing.
  
  
  METHODS
  Ulcer exudates were collected from patients with venous leg ulcers (n = 30). Healing was defined as complete re-epithelialization within 6 months of compression therapy. Time-resolved fluorescence immunoassays were validated for quantification of suPAR and its fragments in ulcer exudates. The effect of exudates on keratinocyte migration was analyzed by an in vitro scratch assay.
  
  
  RESULTS
  Ulcer exudates from patients who healed (n = 9) had approximately threefold higher levels of intact suPAR (P = .005), twofold higher levels of suPARI (P = .03), and approximately threefold higher levels suPARII-III (P < .0001) compared with nonhealers (n = 21). Exudate from healing ulcers stimulated keratinocyte migration (P = .02), whereas depletion of suPAR from exudates resulted in cell apoptosis.
  
  
  CONCLUSIONS
  We conclude that suPAR and its fragments are present in the environs of venous ulcers and may act as indicators of the propensity of venous ulcers to heal, with suPARII-III being the best discriminator. We speculate that suPAR and its fragments may have a role in the maintenance of an optimal ulcer-healing environment.
authors.affiliation: King's College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at GSTT and King's College London, Academic Department of Vascular Surgery, Cardiovascular Division, St Thomas' Hospital, London, United Kingdom.
authors.forename: Anwar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: King's College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at GSTT and King's College London, Academic Department of Vascular Surgery, Cardiovascular Division, St Thomas' Hospital, London, United Kingdom.
authors.forename: Prakash
authors.initials: P
authors.lastname: Saha
authors.affiliation: King's College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at GSTT and King's College London, Academic Department of Vascular Surgery, Cardiovascular Division, St Thomas' Hospital, London, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Evans
authors.affiliation: Finsen Laboratory, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Tine
authors.initials: T
authors.lastname: Thurison
authors.affiliation: Finsen Laboratory, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Hoyer-Hansen
authors.affiliation: King's College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at GSTT and King's College London, Academic Department of Vascular Surgery, Cardiovascular Division, St Thomas' Hospital, London, United Kingdom.
authors.forename: Ashish
authors.initials: A
authors.lastname: Patel
authors.affiliation: King's College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at GSTT and King's College London, Academic Department of Vascular Surgery, Cardiovascular Division, St Thomas' Hospital, London, United Kingdom.
authors.forename: Bijan
authors.initials: B
authors.lastname: Modarai
authors.affiliation: King's College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at GSTT and King's College London, Academic Department of Vascular Surgery, Cardiovascular Division, St Thomas' Hospital, London, United Kingdom. Electronic address: alberto.smith@kcl.ac.uk.
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
mesh_terms: D006801:Humans; D062326:Re-Epithelialization; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D014647:Varicose Ulcer / Q000097:blood* / Q000503:physiopathology
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator