Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin
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...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Beom Jun Kim Noo Ri Lee Chung Hyeok Lee Young Bin Lee Sung Jay Choe Solam Lee Hyun Jee Hwang Eunjung Kim Gareth G. Lavery Kyong-Oh Shin Kyungho Park Eung Ho Choi |
| author_facet | Beom Jun Kim Noo Ri Lee Chung Hyeok Lee Young Bin Lee Sung Jay Choe Solam Lee Hyun Jee Hwang Eunjung Kim Gareth G. Lavery Kyong-Oh Shin Kyungho Park Eung Ho Choi |
| author_sort | Beom Jun Kim |
| collection | DOAJ |
| description | 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. |
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| language | English |
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| publishDate | 2021-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bc66539833224cbf8b51d10ebd83a01d2023-11-21T21:43:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211575010.3390/ijms22115750Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged SkinBeom Jun Kim0Noo Ri Lee1Chung Hyeok Lee2Young Bin Lee3Sung Jay Choe4Solam Lee5Hyun Jee Hwang6Eunjung Kim7Gareth G. Lavery8Kyong-Oh Shin9Kyungho Park10Eung Ho Choi11Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaInstitute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UKDepartment of Food Science and Nutrition, Convergence Program of Materials Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition, Convergence Program of Materials Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaInactive 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.https://www.mdpi.com/1422-0067/22/11/5750barrier functionskin aging11-beta-hydroxysteroid dehydrogenase type 1glucocorticoidsepidermal lipids |
| spellingShingle | Beom Jun Kim Noo Ri Lee Chung Hyeok Lee Young Bin Lee Sung Jay Choe Solam Lee Hyun Jee Hwang Eunjung Kim Gareth G. Lavery Kyong-Oh Shin Kyungho Park Eung Ho Choi Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin International Journal of Molecular Sciences barrier function skin aging 11-beta-hydroxysteroid dehydrogenase type 1 glucocorticoids epidermal lipids |
| title | Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin |
| title_full | Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin |
| title_fullStr | Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin |
| title_full_unstemmed | Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin |
| title_short | Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin |
| title_sort | increased expression of 11β hydroxysteroid dehydrogenase type 1 contributes to epidermal permeability barrier dysfunction in aged skin |
| topic | barrier function skin aging 11-beta-hydroxysteroid dehydrogenase type 1 glucocorticoids epidermal lipids |
| url | https://www.mdpi.com/1422-0067/22/11/5750 |
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