Matrix metalloproteinase-9 delays wound healing in a murine wound model.

Abstract

BACKGROUND:

Metalloproteinase-9 (MMP-9) is a type IV collagenase found at elevated levels in chronic wounds. As wounds heal, MMP-9 diminishes. In this study, we investigated whether MMP-9 directly contributes to chronic wound pathogenesis.

METHODS:

Recombinant proMMP-9 was prepared using immortalized keratinocytes transduced by a lentivirus. ProMMP-9 was purified from cell culture media and activated using 4-aminophenylmercuric acetate. Active MMP-9 was then suspended in xanthan gum to a concentration paralleling that found in human chronic wounds. Two parallel 6-mm punch biopsies were made on the backs of C57BL mice. Wounds were treated daily with MMP-9 or vehicle. Wound areas were measured and tissues examined by densitometry, real-time RT-PCR, histology, and immunohistochemistry at days 7, 10, and 12.

RESULTS:

Exogenous MMP-9, at the level found within chronic wounds, delayed wound healing in this animal model. By 7 days, wounds in the MMP-9-injected group were 12% larger than control wounds (P = .008). By day 12, wounds in the MMP-9-injected group were 25% larger than those of the control group (P = .03). Histologic examination shows that high levels of active MMP-9-impaired epithelial migrating tongues (P = .0008). Moreover, consistent with elevated MMP-9, the collagen IV in the leading edge of the epithelial tongue was diminished.

CONCLUSION:

MMP-9 appears to directly delay wound healing. Our data suggests that this may occur through interference with re-epithelialization. We propose that MMP-9 interferes with the basement membrane protein structure, which in turn impedes keratinocyte migration, attachment, and the reestablishment of the epidermis.

• Authors: Matthew J Reiss, Yan-Ping Han, Edwin Garcia, Mytien Goldberg, Hong Yu, Warren L Garner
• Journal: Surgery (Surgery) Vol. 147 Issue 2 Pg. 295-302 (Feb 2010) ISSN: 1532-7361 [Electronic] United States
• PMID: 20004432 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Mosby, Inc. All rights reserved.

Chemical References

• Enzyme Precursors
• Recombinant Proteins
• pro-matrix metalloproteinase 9
• Matrix Metalloproteinase 9

Topics

• Animals
• Basement Membrane (drug effects, pathology)
• Blotting, Western
• Cell Movement (drug effects)
• Electrophoresis, Polyacrylamide Gel
• Enzyme Precursors (pharmacology)
• Epithelium (drug effects, pathology)
• Matrix Metalloproteinase 9 (metabolism, pharmacology)
• Mice
• Mice, Inbred C57BL
• Recombinant Proteins (pharmacology)
• Skin (injuries)
• Wound Healing (drug effects, physiology)