Increased glucocorticoid activation during mouse skin wound healing.
J Endocrinol
; 221(1): 51-61, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24464022
ABSTRACT
Glucocorticoid (GC) excess inhibits wound healing causing increased patient discomfort and infection risk. 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activates GCs (converting 11-dehydrocorticosterone to corticosterone in rodents) in many tissues including skin, where de novo steroidogenesis from cholesterol has also been reported. To examine the regulation of 11ß-HSD1 and steroidogenic enzyme expression during wound healing, 5âmm wounds were generated in female SKH1 mice and compared at days 0, 2, 4, 8, 14, and 21 relative to unwounded skin. 11ß-HSD1 expression (mRNA and protein) and enzyme activity were elevated at 2 and 4 days post-wounding, with 11ß-HSD1 localizing to infiltrating inflammatory cells. 11ß-HSD2 (GC-deactivating) mRNA expression and activity were undetectable. Although several steroidogenic enzymes displayed variable expression during healing, expression of the final enzyme required for the conversion of 11-deoxycorticosterone to corticosterone, 11ß-hydroxylase (CYP11B1), was lacking in unwounded skin and post-wounding. Consequently, 11-deoxycorticosterone was the principal progesterone metabolite in mouse skin before and after wounding. Our findings demonstrate that 11ß-HSD1 activates considerably more corticosterone than is generated de novo from progesterone in mouse skin and drives GC exposure during healing, demonstrating the basis for 11ß-HSD1 inhibitors to accelerate wound repair.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenômenos Fisiológicos da Pele
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Cicatrização
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Glucocorticoides
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article