Hyperglycemia-activated 11ß-hydroxysteroid dehydrogenase type 1 increases endoplasmic reticulum stress and skin barrier dysfunction.
Sci Rep
; 13(1): 9206, 2023 06 06.
Article
em En
| MEDLINE
| ID: mdl-37280272
ABSTRACT
The diabetes mellitus (DM) skin shows skin barrier dysfunction and skin lipid abnormality, similar to conditions induced by systemic or local glucocorticoid excess and aged skin. Inactive glucocorticoid (GC) is converted into active glucocorticoid by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). Hyperglycemia in DM and excessive GC are known to increase endoplasmic reticulum (ER) stress. We hypothesized that hyperglycemia affects systemic GC homeostasis and that the action of skin 11ß-HSD1 and GC contributes to increased ER stress and barrier defects in DM. We compared 11ß-HSD1, active GC, and ER stress between hyperglycemic and normoglycemic conditions in normal human keratinocytes and db/db mice. 11ß-HSD1 and cortisol increased with time in keratinocyte culture under hyperglycemic conditions. 11ß-HSD1 siRNA-transfected cells did not induce cortisol elevation in hyperglycemic condition. The production of 11ß-HSD1 and cortisol was suppressed in cell culture treated with an ER stress-inhibitor. The 14-week-old db/db mice showed higher stratum corneum (SC) corticosterone, and skin 11ß-HSD1 levels than 8-week-old db/db mice. Topical 11ß-HSD1 inhibitor application in db/db mice decreased SC corticosterone levels and improved skin barrier function. Hyperglycemia in DM may affect systemic GC homeostasis, activate skin 11ß-HSD1, and induce local GC excess, which increases ER stress and adversely affects skin barrier function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
11-beta-Hidroxiesteroide Desidrogenase Tipo 1
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Estresse do Retículo Endoplasmático
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Hiperglicemia
Limite:
Aged
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Animals
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Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2023
Tipo de documento:
Article