title: Possible involvement of gelatinases in basement membrane damage and wrinkle formation in chronically ultraviolet B-exposed hairless mouse.
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.
authors.affiliation: Skincare Ingredient Research Laboratories, Shiseido Material Development Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama 224-8558, Japan. shinji.inomata@to.shiseido.co.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Inomata
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Amano
authors.forename: Keiko
authors.initials: K
authors.lastname: Takada
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsunenaga
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kohno
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000473:pathology / Q000528:radiation effects; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D015595:Skin Aging / Q000502:physiology / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D006877:Hydroxamic Acids; C115088:CGS 27023; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9