| First Author | Tiganescu A | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 7 | Pages | 3051-60 |
| PubMed ID | 23722901 | Mgi Jnum | J:201433 |
| Mgi Id | MGI:5514101 | Doi | 10.1172/JCI64162 |
| Citation | Tiganescu A, et al. (2013) 11beta-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects. J Clin Invest 123(7):3051-60 |
| abstractText | 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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11beta-HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11beta-HSD1 KO mouse skin phenotype. 11beta-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 11beta-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 11beta-HSD1 inhibitor treatment accelerated healing of full-thickness mouse dorsal wounds, with improved healing also observed in aged 11beta-HSD1 KO mice. These findings suggest that elevated 11beta-HSD1 activity in aging skin leads to increased local GC generation, which may account for adverse changes occurring in the elderly, and 11beta-HSD1 inhibitors may be useful in the treatment of age-associated impairments in dermal integrity and wound healing. |
