International Journal of Molecular Sciences | |
Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin | |
BeomJun Kim1  Eunjung Kim1  SungJay Choe1  NooRi Lee1  HyunJee Hwang1  ChungHyeok Lee1  YoungBin Lee1  EungHo Choi1  Solam Lee1  Kyungho Park2  Kyong-Oh Shin2  GarethG. Lavery3  | |
[1] Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea;Department of Food Science and Nutrition, Convergence Program of Materials Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, Korea;Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK; | |
关键词: barrier function; skin aging; 11-beta-hydroxysteroid dehydrogenase type 1; glucocorticoids; epidermal lipids; | |
DOI : 10.3390/ijms22115750 | |
来源: DOAJ |
【 摘 要 】
Inactive cortisone is converted into active cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11β-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11β-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11β-HSD1 knockout mice (n = 11), 11β-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11β-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11β-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.
【 授权许可】
Unknown