Differential effects of acute and chronic wound fluids on urokinase‐type plasminogen activator, urokinase‐type plasminogen activator receptor, and tissue‐type plasminogen activator in cultured human keratinocytes and fibroblasts

Abstract

The effect of wound fluids collected from acute well-healing wounds and chronic nonhealing venous leg ulcers on the plasminogen activation system of keratinocyte and fibroblast cell cultures was studied in a simplified wound-healing model. Acute wound fluid was collected from donor sites of split skin grafts at different time points representing the progressive healing of the wound. Urokinase-type plasminogen activator, tissue-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor 1 expression were studied. The methods used were immunocapture assay and immunocytochemistry. The results indicated that the later the acute wound fluid was collected, the greater the urokinase-type plasminogen activator and the lower the plasminogen inhibitor-1 level in treated cells. In contrast, the level of urokinase-type plasminogen activator receptor remained stable irrespective of wound fluid treatment. Immunostaining for urokinase-type plasminogen activator of acute wound fluid-treated cells showed a disseminated punctate pattern over the cell surface, but with chronic wound fluid, urokinase-type plasminogen activator was localized to focal contacts. Our findings support the view that in the acute wound environment the plasminogen activator system is proteolytically active and that in chronic leg ulcers urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor may also be organized for cell adhesion and migration.

Dysregulated repair in asthmatic paediatric airway epithelial cells: the role of plasminogen activator inhibitor‐1

“…The effect of gene silencing in pAEC AA was more difficult to assess due to the already reduced rate of repair observed in these cells. Previous work performed in keratinocytes has established the association of PAI‐1 expression and leading wound edges [52–54] and, more recently, Marquerlot et al [13] have shown in alveolar epithelial cells that the availability of matrix‐bound‐PAI‐1 is required for efficient healing. Moreover, immediately after wounding, PAI‐1 was shown to be dramatically increased in the newly deposited matrix at the leading edge of wounds.…”

Microdialysis—A Model for Studying Chronic Wounds

“…The test limb is maintained dependent for between 2 and 5 hours and the fluid that collects under the film aspirated using a sterile needle and syringe. 32,33 The occlusion technique has been used to collect fluid from chronic wounds, but it has also been applied to acute wounds, such as at skin donor sites. A major disadvantage of this technique is the time required to accumulate sufficient wound fluid for analysis.…”

Cigarette smoke condensate stimulates urokinase production through the generation of reactive oxygen species and activation of the mitogen activated protein kinase pathways in human gingival fibroblasts

“…Urokinase‐type plasminogen activator is expressed by gingival fibroblasts during wound healing and in periodontitis‐affected gingival tissues (8–10). It has been observed that altered production of urokinase‐type plasminogen activator may lead to aberrant wound repair or to the perpetuation of chronic inflammatory reactions in several diseases or conditions in which connective tissue remodeling plays a significant role (9,11,12). Therefore, factors regulating the production of urokinase‐type plasminogen activator may critically modulate the evolution of tissue repair and inflammation.…”