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- Title
11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects.
- Authors
Tiganescu, Ana; Tahraní, Abd A.; Morgan, Stuart A.; Otranto, Marcela; Desmoulière, Alexis; Abrahams, Lianne; Hassan-Smith, Zaki; Walker, Elizabeth A.; Rabbitt, Elizabeth H.; Cooper, Mark S.; Amrein, Kurt; Lavery, Gareth G.; Stewart, Paul M.
- 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.
- Publication
Journal of Clinical Investigation, 2013, Vol 123, Issue 7, p3051
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI64162