Increased expression of 11β-hydroxysteroid dehydrogenase type 1 contributes to epidermal permeability barrier dysfunction in aged skin

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

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Abstract

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.

Original languageEnglish
Article number5750
JournalInternational journal of molecular sciences
Volume22
Issue number11
DOIs
Publication statusPublished - 2021 Jun 1

Bibliographical note

Funding Information:
Funding: This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korea government (MEST; grant No. NRF-2018R1A2B2005002).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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