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Effects of Recombinant Human Tissue Inhibitor of Metalloproteinases‐2 (rh‐TIMP‐2) on Migration of Epidermal Keratinocytes In vitro and Wound Healing In vivo
Author(s) -
Terasaki Kenjiro,
Kanzaki Tamotsu,
Aoki Takanori,
Iwata Kazushi,
Saiki Ikuo
Publication year - 2003
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2003.tb00367.x
Subject(s) - wound healing , matrix metalloproteinase , in vitro , in vivo , cell migration , chemistry , recombinant dna , tissue inhibitor of metalloproteinase , human skin , medicine , pharmacology , immunology , biology , biochemistry , genetics , microbiology and biotechnology , gene
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 μg/20 μl/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 μg/wound) in diabetic mice (n=6), and the optimal concentration was 10–20 μg 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.