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Alpha1-antichymotrypsin activity correlates with and may modulate matrix metalloproteinase-9 in human acute wounds
Matthew J Reiss1, Yuan-Ping Han, Warren L Garner
1Division of Plastic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Abstract:
Matrix metalloproteinase-9 (MMP-9) plays a central role in many physiologic processes including acute and the chronic wounds. MMP-9 is not routinely expressed in healthy tissues but is promptly expressed as a proenzyme and converted into active enzyme after tissue injury. The mechanisms involved, including the activators and inhibitors for this enzyme in human tissue remain largely obscure. We recently identified alpha1-antichymotrypsin (alpha1-ACT), an acute phase factor, as a potent inhibitor controlling activation of pro-MMP-9 by human skin. The aim of this study is to establish the clinical relevance of the inhibitor in cutaneous wound healing. Fluids from acute burn blisters and conditioned media from skin explants of burn patients were analyzed. We observed that the presence pro-MMP-9 and its activation correlated with the proximity to and degree of injury. Early after trauma, massive levels of wound alpha1-ACT were associated with an absence of pro-MMP-9 activation. Conversely, the active MMP-9 occurs simultaneously with inactivation of alpha1-ACT. Our results suggest a role for alpha1-ACT as a physiologic inhibitor of MMP-9 activation in human wound healing.
Insights
Alpha1-antichymotrypsin (alpha1-ACT) inhibits matrix metalloproteinase-9 (MMP-9) activation in human wound healing. This study shows alpha1-ACT levels correlate with MMP-9 activity, suggesting its clinical relevance in wound repair.
Area of Science:
- Biochemistry
- Dermatology
- Wound Healing Research
Background:
- Matrix metalloproteinase-9 (MMP-9) is crucial in physiological processes, including wound healing.
- MMP-9 is upregulated following tissue injury but its activators and inhibitors in human tissues are not fully understood.
- Alpha1-antichymotrypsin (alpha1-ACT) was recently identified as a potent inhibitor of pro-MMP-9 activation.
Purpose of the Study:
- To investigate the clinical relevance of alpha1-ACT as an inhibitor of MMP-9 in cutaneous wound healing.
- To analyze the relationship between MMP-9 activation and alpha1-ACT levels in human wound fluids and skin explants.
Main Methods:
- Analysis of wound fluids from acute burn blisters.
- Analysis of conditioned media from skin explants of burn patients.
- Assessment of pro-MMP-9 and active MMP-9 levels in relation to alpha1-ACT concentrations.
Main Results:
- Pro-MMP-9 presence and activation correlated with injury proximity and severity.
- High early levels of wound alpha1-ACT were associated with absent pro-MMP-9 activation.
- Active MMP-9 was detected concurrently with alpha1-ACT inactivation.
Conclusions:
- Alpha1-antichymotrypsin (alpha1-ACT) acts as a physiological inhibitor of MMP-9 activation in human wound healing.
- The findings suggest a significant role for alpha1-ACT in regulating MMP-9 activity during the wound repair process.
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