Backgrounds/Objectives: Cathepsin D plays an important part in maintaining a normal skin barrier. Our previous study found that cathepsin D decreased in chronic photodamaged skin. This study investigated the cathepsin D content change in the stratum corneum (SC) and the repairing role of cathepsin D in chronic photodamaged skin barrier via the application of cathepsin D gel. Methods: Cathepsin D gel (0.001%) was applied to chronic photodamaged (sun-exposed forearm) human skin on identical sites (1 cm²/area) twice daily for 2 weeks. At 30 min and at 1, 3, 7, and 14 days, skin hydration and transepidermal water loss (TEWL) average values were detected via noninvasive skin detection equipment. Cathepsin D and transglutaminase (TGase)-1 in the skin sublayers were separated and detected via tape stripping, ELISA and Western blot. Results: After 2 weeks of cathepsin D gel application, the skin moisture value increased from 86.8 ± 1.2 to 95.2 ± 2.7 (p < 0.05), while TEWL decreased from 17.88 ± 1.87 to 11.58 ± 2.14 (p < 0.05). Cathepsin D protein was detected in the upper epidermis (12.6 ± 2.6 ng/cm2), mid-epidermis (8.4 ± 0.8 ng/cm2) and deep epidermis (16.2 ± 2.6 ng/cm2) in the cathepsin D gel group compared to the control group (2.2 ± 0.7, 3.0 ± 1.1 and 3.85 ± 1.4 ng/cm2, respectively; p < 0.05). TGase-1 enzyme expression was upregulated 2.54 ± 0.19 times in the matrix gel-treated skin. Conclusions: These data suggest that cathepsin D gel could increase the SC cathepsin D content and repair the epidermal barrier in chronic photodamaged skin. The mechanism might be related to increasing TGase-1 expression and activity. © 2014 S. Karger AG, Basel

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