1. Skincare Ingredient Research Laboratories, Shiseido Life Science Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama 224-8558, Japan;
2. ^*Discovery Research Laboratories, Shiseido Material Development Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama 224-8558, Japan;
3. ^†Material & Formulation Research Laboratories, Shiseido Material Development Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama 224-8558, Japan;
4. ^‡Skin Biology Research Laboratories, Shiseido Life Science Research Center; 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan

Correspondence: Dr Shinji Inomata, Skincare Ingredient Research Laboratories, Shiseido Life Science Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama 224-8558, Japan. Email: shinji.inomata@to.shiseido.co.jp

Received 10 July 2002; Revised 12 September 2002; Accepted 16 September 2002.

Abstract

A number of studies indicate that matrix metalloproteinase might be involved in photoaging, but little is known about their direct contribution to ultraviolet-induced histologic and morphologic changes in the skin in vivo. This study reports the relationship between changes of matrix metalloproteinase activities and ultraviolet B-induced skin changes in hairless mouse. The role of matrix metalloproteinase in the skin changes was studied by topical application of a specific matrix metalloproteinase inhibitor. The backs of mice were exposed to ultraviolet B three times a week for 10 wk. Histologic studies showed that the basement membrane structure was damaged, with epidermal hyperplasia, in the first 2 wk of ultraviolet B irradiation, followed by the appearance of wrinkles, which gradually extended in the latter half of the ultraviolet B irradiation period. We observed enhancement of type IV collagen degradation activity, but not collagenase or matrix metalloproteinase-3 activity, in extracts of ultraviolet B-irradiated, wrinkle-bearing skin. Gelatin zymographic analysis revealed that gelatinases, matrix metalloproteinase-9 and matrix metalloproteinase-2, were significantly increased in the extract. In situ zymographic study clarified that the activity was specifically localized in whole epidermis of ultraviolet B-irradiated, wrinkled skin in comparison with normal skin. The activity was induced around the basal layer of the epidermis by a single ultraviolet exposure of at least one minimal erythema dose. Furthermore, topical application of a specific matrix metalloproteinase inhibitor, CGS27023A, inhibited ultraviolet B-induced gelatinase activity in the epidermis, and its repeated application prevented ultraviolet B-induced damage to the basement membrane, as well as epidermal hyperplasia and dermal collagen degradation. Ultraviolet B-induced wrinkles were also prevented by administration of the inhibitor. These results, taken together, suggest that ultraviolet B-induced enhancement of gelatinase activity in the skin contributes to wrinkle formation through the destruction of basement membrane structure and dermal collagen in chronically ultraviolet B-exposed hairless mouse, and thus topical application of matrix metalloproteinase inhibitors may be an effective way to prevent ultraviolet B-induced wrinkle formation.