光老化によるシワの形成機序とその予防
2003 年 18 巻 2 号 p. 157-164
詳細
2003 年 18 巻 2 号 p. 157-164
A series of our studies demonstrated that wrinkling on the human face is initiated at the eye corner which is the most frequently sun-exposed area. The depth of the wrinkling was found to be paralleled by the diminished elastic property in the same area, indicating that a significant decrease in the skin elasticity is mainly responsible for the formation of wrinkling. In our studies using rat hind limb skins for elucidating the causative factors of the reduced elasticity, we found that wrinkle formation in the skin following long-term UVB irradiation was accompanied by decreases in skin elasticity and the concomitant curling of elastic fibers in the dermis which suggested that the tortuosity of dermal elastic fibers is an important determinant in reducing the skin elasticity. Since the damage in three dimensional elastic fiber structures seems to be attributable to the partial digestion by elastases, the degradative enzymes for elastic fibers, whose activities in the dermis were enhanced by repeated UVB irradiations, we determined whether the inhibition of elastase activity in vivo would prevent the damage of dermal elastic fibers and might eradicate wrinkle formation associated with the loss of skin elasticity. Because the major elastase in the skin under non-inflammatory onditions is skin fibroblast elastase, we used a specific inhibitor of that enzyme to assess its biological role in wrinkle formation. The hind limb skins of Sprague-Dawley rats or hairless mice were irradiated with UVB at a suberythemal dose 3 times a week for 6 weeks. During that period, 0.1-10.0 mM N-phenetylphosphonyl-leucyl-tryptophane (NPLT), an inhibitor of skin fibroblast elastase, was applied topically 5 times a week. NPLT application at concentrations of 0.1-1.0 mM eradicated wrinkle formation in a dose-dependent manner, with a peak for inhibition at 1.0mM. This inhibition was accompanied by a continued low tortuosity of dermal elastic fibers and a maintenance of skin elasticity. These findings suggest that skin fibroblast elastase plays an essential role in the degeneration and /or tortuosity of elastic fibers induced by cumulative UVB irradiation and that its inhibition would provide a desirable model for preventing sun-induced wrinkling. [Skin Cancer (Japan) 2003; 18: 157-164]
