Increased glucocorticoid activation during mouse skin wound healing

Area of Science:

• Endocrinology
• Wound Healing Research
• Dermatology

Background:

• Glucocorticoid (GC) excess negatively impacts wound healing, increasing patient discomfort and infection risk.
• 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates GCs in tissues like skin, where steroidogenesis also occurs.
• Understanding GC regulation in skin is crucial for improving wound repair.

Purpose of the Study:

• To investigate the regulation of 11β-HSD1 and steroidogenic enzymes during the wound healing process in mouse skin.
• To determine the role of 11β-HSD1 in driving GC exposure in healing skin.
• To explore the potential of targeting 11β-HSD1 for enhanced wound healing.

Main Methods:

• Generated 5mm wounds in female SKH1 mice.
• Analyzed unwounded and wounded skin at multiple time points (0, 2, 4, 8, 14, 21 days) for gene and protein expression, and enzyme activity.
• Quantified 11β-HSD1, 11β-HSD2, and key steroidogenic enzymes, including CYP11B1.

Main Results:

• 11β-HSD1 expression and activity significantly increased at 2 and 4 days post-wounding, localizing to inflammatory cells.
• 11β-HSD2 expression and activity were undetectable.
• CYP11B1 was absent, and 11-deoxycorticosterone was the primary metabolite, indicating 11β-HSD1 drives GC activation during healing.

Conclusions:

• 11β-HSD1 activation of corticosterone significantly exceeds de novo steroidogenesis in mouse skin during healing.
• Elevated 11β-HSD1 activity drives GC exposure in healing skin, explaining impaired wound repair.
• Targeting 11β-HSD1 presents a therapeutic strategy to accelerate wound healing.