Projects per year
Abstract
Glucocorticoid (GC) excess adversely affects skin integrity, inducing thinning and impaired wound healing. Aged skin, particularly that which has been photo-exposed, shares a similar phenotype. Previously, we demonstrated age-induced expression of the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11β-HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11β-HSD1 KO mouse skin phenotype. 11β-HSD1 activity was elevated in aged human and mouse skin and in PE compared with donor-matched photo-protected human biopsies. Age-induced dermal atrophy with deranged collagen structural organization was prevented in 11β-HSD1 KO mice, which also exhibited increased collagen density. We found that treatment of HDFs with physiological concentrations of cortisol inhibited rate-limiting steps in collagen biosynthesis and processing. Furthermore, topical 11β-HSD1 inhibitor treatment accelerated healing of full-thickness mouse dorsal wounds, with improved healing also observed in aged 11β-HSD1 KO mice. These findings suggest that elevated 11β-HSD1 activity in aging skin leads to increased local GC generation, which may account for adverse changes occurring in the elderly, and 11β-HSD1 inhibitors may be useful in the treatment of age-associated impairments in dermal integrity and wound healing.
Original language | English |
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Pages (from-to) | 3051-3060 |
Journal | Journal of Clinical Investigation |
Volume | 123 |
Issue number | 7 |
DOIs | |
Publication status | Published - 3 Jun 2013 |
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Dive into the research topics of '11β-hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects'. Together they form a unique fingerprint.Projects
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Investigating Hexose-6-Phosphate Dehydrogenase in the Control of Skeletal Muscle Function and Carbohydrate Metabolism
Lavery, G.
Biotechnology & Biological Sciences Research Council
1/09/09 → 31/08/14
Project: Research Councils