Activities of the Matrix Metalloproteinase Stromelysin-2 (MMP-10) in Matrix Degradation and Keratinocyte Organization in Wounded Skin

• DOI: 10.1091/mbc.e04-02-0109
• Publication Date: 2004-09-16T00:28:22Z
• Authors: Monika Krampert; Wilhelm Bloch; Takako Sasaki; Philippe Bugnon; Thomas Rülicke; Eckhard Wolf; Monique Aumailley; William C. Parks; Sabine Werner
• Keywords: Keratinocytes; Male; 0303 health sciences; Integrin beta1; Gene Expression; Metalloendopeptidases; Apoptosis; Mice, Transgenic; Epithelium; Extracellular Matrix; Mice; 03 medical and health sciences; Matrix Metalloproteinase 10; Cell Movement; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Mutation; Animals; Humans; Female; Cell Adhesion Molecules; Cells, Cultured

The matrix metalloproteinase stromelysin-2 is expressed in keratinocytes of the epithelial tongue of skin wounds, suggesting a role in keratinocyte migration. Here, we show that stromelysin-2 enhances migration of cultured keratinocytes. To gain insight into the in vivo activities of stromelysin-2 in epithelial repair, we generated transgenic mice expressing a constitutively active stromelysin-2 mutant in keratinocytes. These animals had no alterations in skin architecture, and the healing rate of skin wounds was normal. Histologically, however, we found abnormalities in the organization of the wound epithelium. Keratinocytes at the migrating epidermal tip were scattered in most sections of mice with high expression level, and there was a reduced deposition of new matrix. In particular, the staining pattern of laminin-5 at the wound site was altered. This may be due to proteolytic processing of laminin-5 by stromelysin-2, because degradation of laminin-5 by this enzyme was observed in vitro. The inappropriate matrix contact of keratinocytes was accompanied by aberrant localization of β1-integrins and phosphorylated focal adhesion kinase, as well as by increased apoptosis of wound keratinocytes. These results suggest that a tightly regulated expression level of stromelysin-2 is required for limited matrix degradation at the wound site, thereby controlling keratinocyte migration.