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Updated: May 11, 2026
07:32
Human Ex vivo Wound Model and Whole-Mount Staining Approach to Accurately Evaluate Skin Repair
Published on: February 17, 2021
11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects.
Ana Tiganescu1, Abd A Tahrani, Stuart A Morgan
1Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
The Journal of Clinical Investigation
|June 1, 2013
Summary
Elevated 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity in aging skin increases local glucocorticoids, causing thinning and poor wound healing. Inhibiting 11β-HSD1 may improve skin health and repair in older individuals.
Area of Science:
- Dermatology
- Endocrinology
- Aging Research
Background:
- Glucocorticoid excess negatively impacts skin integrity and wound healing.
- Aging skin, especially photo-aged skin, exhibits similar detrimental changes.
- Previous studies indicated age-induced 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression in fibroblasts.
Purpose of the Study:
- To investigate 11β-HSD1 levels in aged human and mouse skin.
- To determine the role of 11β-HSD1 in age-associated skin changes and wound healing.
- To evaluate the therapeutic potential of 11β-HSD1 inhibition for skin aging and repair.
Main Methods:
- Measured 11β-HSD1 levels in human skin biopsies from young and older volunteers.
- Examined skin phenotype in aged 11β-HSD1 knockout (KO) mice.
- Assessed collagen biosynthesis in cultured human dermal fibroblasts (HDFs) treated with cortisol.
- Evaluated wound healing in mice treated with topical 11β-HSD1 inhibitors and in aged 11β-HSD1 KO mice.
Main Results:
- 11β-HSD1 activity was elevated in aged human and mouse skin, and photo-exposed skin.
- 11β-HSD1 KO mice showed prevention of age-induced dermal atrophy and improved collagen density.
- Cortisol inhibited collagen processing in HDFs; topical 11β-HSD1 inhibition accelerated wound healing.
- Aged 11β-HSD1 KO mice exhibited improved wound healing.
Conclusions:
- Elevated 11β-HSD1 activity in aging skin increases local glucocorticoid generation, contributing to skin aging.
- Targeting 11β-HSD1 may reverse detrimental skin changes associated with aging.
- 11β-HSD1 inhibitors show promise for treating age-related skin integrity and wound healing impairments.
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