AI Article Synopsis
- uPA and its receptor uPAR play a key role in wound healing by activating proteolytic mechanisms at the cell surface, and soluble forms of uPAR (suPAR and its fragments) are involved in cellular functions important for healing.
- A study analyzed ulcer exudates from 30 patients with venous leg ulcers to assess the levels of suPAR and its fragments and their association with healing outcomes.
- Results showed that exudates from patients who healed had significantly higher levels of suPAR and its fragments, and these exudates promoted keratinocyte migration, suggesting that these proteins could serve as indicators of healing potential in venous ulcers.
Article 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.
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| http://dx.doi.org/10.1016/j.jvsv.2014.08.002 | DOI Listing |
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