Effects of recombinant human tissue inhibitor of metalloproteinases-2 (rh-TIMP-2) on migration of epidermal keratinocytes in vitro and wound healing in vivo.
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 microg/20 microl/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 microg/wound) in diabetic mice (n=6), and the optimal concentration was 10-20 microg 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.
Terasaki
Kenjiro
K
Department of Dermatology, Kagoshima University Faculty of Medicine, Kagoshima, Japan.
Kanzaki
Tamotsu
T
Aoki
Takanori
T
Iwata
Kazushi
K
Saiki
Ikuo
I
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011336:Probability; D011995:Recombination, Genetic; D012016:Reference Values; D012680:Sensitivity and Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000473:pathology
D019716:Tissue Inhibitor of Metalloproteinase-2