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Elevated matrix-metalloproteinase activity in chronic wound fluid

Rayment, Erin A., Shooter, Gary K., George, Graeme A., & Upton, Zee (2006) Elevated matrix-metalloproteinase activity in chronic wound fluid. In 16th European Tissue Repair Society Annual Meeting, Pisa, Italy.

Abstract

Aims

There is much debate surrounding the under- and overexpression of MMPs in chronic wounds. One view is that the overexpression of MMP-3 and MMP-13 correlates with non-healing wounds, whereas active MMPs-1, -2, -9, and -14 are all required for normal wound healing. Others report that elevated levels of MMP-2/-9 are detrimental to wound healing in prolonged environments, and should be inhibited to allow normal repair to occur. Further studies indicate that chronic wound fluid includes high levels of various MMPs, including MMP-1, -2, -3, -8, and -9, leading to the degradation of key elements in the wound healing process. In this study we attempt to simplify these findings using a number of MMP detection strategies and patient samples.

Methods

Chronic wound fluid from six consenting patients was obtained under human ethical approval. Total protein content was standardized across the samples, along with human serum and one acute wound fluid sample. Wound fluid was characterized in the first instance using type I and IV collagen zymography. In addition, these samples were also incubated with increasing concentrations of the specific MMP-inhibitor GM6001 (Chemicon, USA) to confirm that the collagen degrading activity was not due to other proteases. Western blotting with a number of different MMP antibodies has also been performed to confirm the presence of specific MMPs.

Results

Type I collagen zymography demonstrates significant differences between chronic wound fluid and human serum. The elevated levels of MMPs found in chronic wound fluid also result in slightly different profiles between patients. Inhibitor studies reveal that increasing concentrations of GM6001 decrease collagenase activity, leading to complete inhibition of collagen degradation above a 1 mM concentration. Preliminary western blotting results also show similar findings.

Conclusions

In future work we wish to: 1. Correlate specific MMP activity with clinical PUSH scores to determine whether a decrease in activity is directly linked to a healing wound 2. Explore other MMP inhibitors for clinical applications

Impact and interest:

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ID Code: 5698
Item Type: Conference Item (Poster)
Additional Information: For more information, please refer to the conference’s website (see link) or contact the author. Author contact details: g.shooter@qut.edu.au
Additional URLs:
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Dermatology (110304)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Copyright Owner: Copyright 2006 (please consult author)
Deposited On: 01 Dec 2006
Last Modified: 15 Jan 2009 17:16

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