期刊
JOURNAL OF DERMATOLOGY
卷 30, 期 3, 页码 165-172出版社
WILEY
DOI: 10.1111/j.1346-8138.2003.tb00367.x
关键词
tissue inhibitor of metalloproteinases-2 (TIMP-2); keratinocyte; migration; wound healing; animals
类别
Tissue inhibitors of metalloproteinases (TIMP), common inhibitors of matrix proteinases, have cell-promoting activity. We studied the effects of recombinant human tissue inhibitor of metalloproteinases-2 (rh-TIMP-2) on the migration of normal human epidermal keratinocytes (NHEK). An in vitro migration assay revealed that rh-TIMP-2 enhanced random migration (up to 170%, p < 0.05) in a dose-dependent manner. When we applied rh-TIMP-2 solution (20 mug/20 mul/wound) daily to full-thickness wounds made with an 8-mm punch on the backs of healthy (n = 8), aged (n = 9), and diabetic (n = 15) rodents, we observed faster wound closure (p < 0.05) than in vehicle-treated controls. Accelerated wound closure was dose-dependent (0-20 mug/wound) in diabetic mice (n = 6), and the optimal concentration was 10-20 mug of rh-TIMP-2/wound. Histological examinations performed on days 0, 5, 10, 15, and 20 in diabetic mice revealed faster migration of epidermal keratinocytes from wound edges. These results suggest that rh-TIMP-2 plays an important role in wound healing.
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