Related Experiment Videos
Plasminogen activation in venous leg ulcers
Y Herouy1, D Trefzer, M O Hellstern
1Department of Dermatology, University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. herouy@haut.ukl.uni-freiburg.de
Background:
Venous leg ulceration results from chronic venous insufficiency of the lower extremities. We recently showed that matrix metalloproteinase (MMP) -2 plays a major part in the pathogenesis of venous leg ulcers. In vitro activation of recombinant MMP-2 is controlled by the activity of the urokinase-type plasminogen activator (uPA), which acts as a fibrin-independent plasminogen activator. The activity of MMP-2 is potentiated by binding of uPA to the uPA receptor (uPAR).
Objectives:
We aimed to clarify the role of plasminogen activation in venous leg ulcers.
Methods:
The expression of uPA, uPAR, the tissue-type plasminogen activator, and plasminogen activator inhibitor (PAI) -1 and PAI-2 was investigated using reverse transcription followed by polymerase chain reaction and Western blotting.
Results:
These provided direct evidence of elevated expression of uPA and uPAR at the mRNA and protein levels in venous leg ulcers, in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and uPAR was detected. Fibrin zymography showed significantly elevated endogenous uPA activity in venous leg ulcers in comparison with healthy controls.
Conclusions:
Our findings indicate venous leg ulcers to be characterized by elevated plasminogen activation, suggesting that this enzyme cascade plays a crucial part in maintaining proteolytic activity in venous leg ulcers.
Insights
Venous leg ulcers show increased urokinase-type plasminogen activator (uPA) and its receptor (uPAR). This suggests plasminogen activation is key to the ulcer
Area of Science:
- Wound healing research
- Biochemistry of tissue repair
- Vascular biology
Background:
- Venous leg ulcers stem from chronic venous insufficiency.
- Matrix metalloproteinase-2 (MMP-2) is implicated in ulcer pathogenesis.
- MMP-2 activation involves urokinase-type plasminogen activator (uPA) and its receptor (uPAR).
Purpose of the Study:
- To investigate the role of plasminogen activation in venous leg ulcers.
- To clarify the expression and activity of key plasminogen activators in ulcer tissue.
Main Methods:
- Analysis of uPA, uPAR, tPA, PAI-1, and PAI-2 expression via RT-PCR and Western blotting.
- Immunohistochemical detection of uPA and uPAR.
- Assessment of endogenous uPA activity using fibrin zymography.
Main Results:
- Elevated mRNA and protein levels of uPA and uPAR in venous leg ulcers compared to healthy skin.
- Increased immunohistochemical staining for uPA and uPAR in ulcer tissue.
- Significantly higher endogenous uPA activity observed in venous leg ulcers.
Conclusions:
- Venous leg ulcers exhibit heightened plasminogen activation.
- This enzyme cascade is crucial for maintaining proteolytic activity in these ulcers.
- Findings suggest targeting plasminogen activation could be a therapeutic strategy.