Controlled proteolysis is needed for cell migration, angiogenesis, and matrix remodeling during normal
wound repair. Our objective has been to investigate how chronic
leg ulcers differ from normally healing
wounds (pinch graft donor sites) with respect to their
metalloproteinase expression patterns. Using in situ hybridization and immunohistochemistry, we found that
collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) were expressed in keratinocytes bordering both acute and chronic
wounds. Unlike MMP-1, signal for
collagenase-3 (MMP-13) was not detected in keratinocytes but exclusively in fibroblasts deep in the
ulcer bed of chronic
wounds, suggesting that while MMP-1 production is important for migration, MMP-13 plays a role in matrix remodeling.
Tissue inhibitor of metalloproteinase (TIMP)-1 was not detected in the epidermis of any chronic
wound sample while it was expressed in keratinocytes bordering normally healing
wounds.
TIMP-3 was abundantly expressed in stromal fibroblast- and macrophage-like cells surrounding vessels and sweat glands in both types of
wounds. Our results suggest that there are no qualitative differences in the expression of MMPs-1, -3 and -10 in the epidermis of chronic vs normally healing
wounds. However, the number of stromal cells expressing MMP-1 and MMP-3 was greater in chronic vs acute
wounds, whereas MMP-10 was never detected in the dermis.
TIMP-1 expression near the basement membrane in acute, but not in chronic,
wounds suggests that the balance between
MMPs and their inhibitors may be altered in poorly healing
wounds. Analogous to chronic cutaneous
wounds, MMP-1 and -3 are abundantly expressed in chronic small and large bowel
ulcers, while the migrating surface epithelium is negative for
TIMP-1 expression.