TY - JOUR
T1 - The soluble urokinase plasminogen activator receptor and its fragments in venous ulcers
AU - Ahmad, Anwar
AU - Saha, Prakash
AU - Evans, Colin
AU - Thurison, Tine
AU - Hoyer-Hansen, Gunilla
AU - Patel, Ashish
AU - Modarai, Bijan
AU - Smith, Alberto
N1 - Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.jvsv.2014.08.002
DO - 10.1016/j.jvsv.2014.08.002
M3 - Journal article
C2 - 26993839
SN - 2213-333X
VL - 3
SP - 190
EP - 197
JO - Journal of Vascular Surgery: Venous and Lymphatic Disorders
JF - Journal of Vascular Surgery: Venous and Lymphatic Disorders
IS - 2
ER -