Activities of the Matrix Metalloproteinase Stromelysin-2 (MMP-10) in Matrix Degradation and Keratinocyte Organization in Wounded Skin
| Autor: | William C. Parks, Eckhard Wolf, Philippe Bugnon, Sabine Werner, Monika Krampert, Wilhelm Bloch, Thomas Rülicke, Monique Aumailley, Takako Sasaki |
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| Rok vydání: | 2004 |
| Předmět: |
Keratinocytes
Male Gene Expression Apoptosis Mice Transgenic Protein Serine-Threonine Kinases Matrix (biology) Biology Matrix metalloproteinase Skin Diseases Epithelium Focal adhesion Extracellular matrix Mice Matrix Metalloproteinase 10 Cell Movement Proto-Oncogene Proteins medicine Animals Humans Phosphorylation Keratinocyte migration Molecular Biology Cells Cultured Skin Wound Healing integumentary system Cell adhesion molecule Integrin beta1 Metalloendopeptidases Articles Cell Biology Protein-Tyrosine Kinases Molecular biology Extracellular Matrix Cell biology medicine.anatomical_structure Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Mutation Wounds and Injuries Female Keratinocyte Wound healing Cell Adhesion Molecules Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Molecular Biology of the Cell. 15:5242-5254 |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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