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Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars
Filippo Renò1, Paola Grazianetti, Maurizio Stella
1Human Anatomy Laboratory, Medical Sciences Department, University of Eastern Piedmont A. Avogadro, Via Solaroli 17, 28100 Novara, Italy.
Objective:
To investigate induction of matrix metalloproteinases (MMPs) during mechanical compression of hypertrophic scars. Mechanical pressure blocks hypertrophy inducted on extracellular matrix in scars by a mechanism that involves MMP-2 (gelatinase A) and MMP-9 (gelatinase B).
Design:
We assayed conditioned media obtained from normotrophic and hypertrophic scars during 24 hours of in vitro mechanical compression using gelatin zymography.
Setting:
Scars from various areas of the bodies of hospitalized patients.
Patients:
We obtained 3 normotrophic and 7 hypertrophic biopsy specimens from 10 patients (5 men and 5 women).
Intervention:
In vitro compression at a pressure of 35 mm Hg/cm(2) for 24 hours.
Main Outcome Measures:
Vitality of scars was analyzed by means of lactic dehydrogenase test; medium samples were collected for zymographic analysis of MMP activity.
Results:
We found MMP-2 in basal (uncompressed) samples from normotrophic and hypertrophic scars. Mechanical compression induced MMP-9 release and activation (range, 86.7%-78.7%) in hypertrophic scars after 4 hours.
Conclusion:
Production, release, and activation of MMP-9 in hypertrophic scars could be an effector mechanism responsible for hypertrophy regression induced by mechanical compression.
Insights
Mechanical compression of hypertrophic scars induces matrix metalloproteinase-9 (MMP-9) release and activation. This MMP-9 activity is key to reducing scar hypertrophy.
Area of Science:
- Biomedical Engineering
- Wound Healing Research
- Dermatological Science
Background:
- Hypertrophic scars result from excessive extracellular matrix deposition.
- Mechanical compression is a known method to reduce scar hypertrophy.
- The underlying molecular mechanisms, particularly involving matrix metalloproteinases (MMPs), are not fully understood.
Purpose of the Study:
- To investigate the induction of matrix metalloproteinases (MMPs) during mechanical compression of hypertrophic scars.
- To elucidate the role of MMP-2 and MMP-9 in the anti-hypertrophic effects of mechanical pressure.
Main Methods:
- Assayed conditioned media from normotrophic and hypertrophic scars under in vitro mechanical compression (35 mm Hg/cm(2) for 24 hours) using gelatin zymography.
- Analyzed scar vitality using a lactic dehydrogenase test.
- Obtained biopsy specimens from 10 patients (3 normotrophic, 7 hypertrophic).
Main Results:
- MMP-2 was detected in basal (uncompressed) samples of both scar types.
- Mechanical compression significantly induced MMP-9 release and activation in hypertrophic scars within 4 hours (86.7%-78.7% increase).
Conclusions:
- The production, release, and activation of MMP-9 in hypertrophic scars appear to be a critical effector mechanism.
- This MMP-9 activity is likely responsible for the regression of hypertrophy observed with mechanical compression.