The Role of Elastases Secreted by Fibroblasts in Wrinkle Formation: Implication Through Selective Inhibition of Elastase Activity¶

Abstract

We have previously demonstrated that decreases in skin elasticity, accompanied by increases in the tortuosity of elastic fibers, are important early events in wrinkle formation. In order to study the role of elastases in the degeneration of elastic fibers during wrinkle formation we examined the effects of an inhibitor of skin fibroblast elastase, N-phenethylphosphonyl-L-leucyl-L-tryptophane (NPLT), on wrinkle formation in hairless mice skin following UV irradiation. Dorsal skins of hairless mice were exposed daily to UV light for 18 weeks at doses of 65-95 mJ/cm2 and treated topically with 100 microL of 1 mM NPLT immediately after each UV irradiation. Wrinkles on dorsal skins were evaluated from week 6 through week 18. The daily exposure of mouse skin to UV light with less than 1 minimal erythemal dose significantly enhanced the activity of elastase in the exposed skin by week 4, and the elevated levels of elastase activity were significantly reduced by the in vitro incubation with NPLT in a dose-dependent manner to a level similar to that in unexposed mice skin, indicating that NPLT can efficiently inhibit the UV-inducible elastase activity. Topical application of NPLT significantly suppressed wrinkle formation when compared with vehicle controls by week 15 of treatment (P < 0.05). Histochemistry of elastic fibers with Orcein staining demonstrated that there were no obvious decreases of the fine elastic fibers in UV-exposed NPLT-treated skin in contrast to their marked decreases in the UV-exposed vehicle-treated skin. These findings suggest that skin fibroblast elastase plays a decisive role in wrinkle formation through the degeneration of elastic fiber.

Mechanistic Effects of Long-Term Ultraviolet B Irradiation Induce Epidermal and Dermal Changes in Human Skin Xenografts

“…4,6,7,9,11,21,22,24,29 Moreover, gene chip analysis indicated a lot of similarities in the comparisons between young versus old skins and our control versus UVB-exposed skins, corroborating the validity of our photodamage or premature photoaging model. Taken together, the present study discloses a novel photodamage model with human skin xenograft that recapitulates mechanisms underlying morphological changes such as wrinkling reported to date, and can be used for the further study of photoaging.…”

“…5,8,10,11,20 On the other hand, it has been reported that the degeneration of these fibers in chronologically and/or photoaged skin stems from an increase in matrix metalloproteinase-12 (MMP-12) and/or elastase, an elastin-degrading enzyme that is produced and secreted by dermal fibroblasts. [21][22][23][24] To date, the mechanisms underlying the alteration of elastin fibers in photoaged skin including their production, accumulation, and degradation are not fully understood.…”

The research of pharmacological activation for Sanguisorbae Radix Fractions as cosmetic material

“…. elastase 저해제는 피부 주름을 개선하는 작용을 나타 내고, ursolic acid등이 elastase 저해제로 이용되고 있다 16) . 그리고 체내의 elastin을 분해하는 백혈구 과립 효소 중의 하 나로 이상조직에서는 효소의 활성이 극히 높아 조직 파괴에 직접적인 원인이 되어 피부의 주름 및 탄력성 소실을 유발한 다 17) .…”

A Study of the Antioxidant Activities and Whitening Activities of Areca semen Extracts as Cosmetic Ingredient

“…이에 따라 식물 등 천연물로부터 얻어지는 기능성 물질들 을 원료로서 이용하려는 연구가 활발히 진행되고 있 다 [1]. 이러한 요구에 대응하여 천연물 특히 한방소재 또는 약용식물을 중심으로 한 미백효과, 노화억제 및 자외선 차단 기능 등 유용한 소재에 대한 개발이 이루 어지고 있다 [2].…”