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/cm 2 and treated topically with 100 L 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 dosedependent 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 Ͻ 0.05). Histochemistry of elastic fibers with Orcein staining demonstrated that there were no obvious decreases of the fine elastic fibers in UV-exposed NPLTtreated 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.

New wrinkles on wrinkling: an 8-year longitudinal study on the progression of expression lines into persistent wrinkles

“…15 These molecular changes result in a decline in the skin's youthful elastic properties which are believed to be fundamental in wrinkle formation. [16][17][18][19][20][21] Kligman et al 1 studied the histology of persistent wrinkles. While the skin showed many of the common histological features appropriate for the subjects' age and body site, they did not observe any remarkable differences in the epidermal or dermal structure between the wrinkle and the surrounding skin, a finding confirmed by Bosset et al 22 and Piérard and Lapière 23 who did find differences in the hypodermal septa.…”

The comparison of the melanin content and UV exposure affecting aging process: seven countries in Asia

“…10,11 UVB exposure induces the expression of fibroblast elastase that degenerate the elastic fiber which plays an important role in maintaining the skin elasticity, and this decreased elasticity by UVB exposure plays a critical role in wrinkle formation. 12 There are some studies that show skin aging progress to differ between Chinese and French women and a significant difference in the wrinkles among China, Japan, and Thailand. 13,14 However, it has almost never been studied for different reasons of skin properties among each county.…”

In the shadow of the wrinkle: experimental models

“…8,9 For example, the inhibition of fibroblast elastase has been shown to protect elastic fibers and to reduce wrinkle formation in Hr mice. 10,11 Efficiency tests for cell injections or laser therapies have also been carried out on the Hr mouse model. 12,13 More recently, Hachiya et al 14 have grafted human abdominal skin on severe combined immunodeficiency (SCID) mice and have used this chimeric mouse model to study the photoaging effects of UVB radiation on human xenografts.…”