Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 31 OC2.7 | DOI: 10.1530/endoabs.31.OC2.7

SFEBES2013 Oral Communications Steroids and thyroid (8 abstracts)

11β-hydroxysteroid dehydrogenase type 1: a role in skin wound healing

Ana Tiganescu , Yoshikazu Uchida , Peter Elias & Walter Holleran


Dermatology, UCSF, San Francisco, California, USA.


Glucocorticoid (GC) excess inhibits wound healing (WH) causing increased patient discomfort and infection risk. The GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates local GC availability in tissues including liver, adipose, and muscle. 11β-HSD1 is also expressed in skin, where studies recently demonstrated increased levels in older donors and a reversal of age-induced dermal atrophy in 11β-HSD1-null mice. However, the role of 11β-HSD1 during WH remains to be elucidated.

Following ethical approval, two 5 mm full-thickness dorsal wounds were generated in female SKH1-HR mice and collected on day 0 (d0), d2, d4, d8 (n=4). 11β-HSD1, cofactor-supplying hexose-6-phosphate dehydrogenase (H6PDH), glucocorticoid receptor (GR) and the differentiation marker filaggrin were analyzed by qPCR (normalized to 18S rRNA). 11β-HSD1 protein was analyzed by Western blot in dispase-separated epidermis/dermis (n=4, normalized with β-actin). Confluent primary mouse keratinocytes were differentiated for 48 h with 1.5 mM calcium±200 nM corticosterone±the GR inhibitor RU486 (n=3 each group).

11β-HSD1 protein increased substantially in full-thickness wounds at d2 relative to d0 and d2 unwounded skin (negligible), was reduced at d4 (detectable exclusively in wounded dermis), and was negligible by d8; qPCR revealed a 14-fold mRNA increase at d2 (vs unwounded, P<0.05), fourfold increase at d4 (P<0.05) decreasing to baseline levels by d8. H6PDH mRNA increased in d4 and d8 wounds (twofold, P<0.05) whilst filaggrin mRNA increased in d8 wounds (1.6-fold, P<0.05). GR mRNA levels were unaffected by wounding.

Increased 11β-HSD1 during early WH suggests GC activation could potentiate subsequent keratinocyte differentiation. Indeed, calcium-treated keratinocytes displayed increased filaggrin and H6PDH mRNA only during GC co-incubation (6- and 12-fold respectively P<0.01), effects blocked by RU486. GR expression was unaffected by differentiation.

Therefore, 11β-HSD1 blockade may accelerate WH by limiting keratinocyte differentiation, promoting proliferation/migration and re-epithelialization, of potential importance in older patients exhibiting elevated basal 11β-HSD1 levels and impaired WH.

Declaration of funding

This work was supported by a US Department of Defence grant W81XWH-11-2-0189.

Article tools

My recent searches

No recent searches.