LICAMM Pre-receptor regulation of glucocorticoid target genes in human skin

Summary

Glucocorticoid (GC) steroid hormones (commonly used to treat inflammatory disorders eg giant cell arteritis - a condition affecting older people) cause many adverse effects in skin including thinning, collagen loss, poor wound healing and increased infection risk. GC are activated by the enzyme 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) and this regulates cell function (e.g. growth, development, signalling) in tissues such as fat, muscle and liver but the effects of 11?-HSD1 in human skin are unknown. Previous research has demonstrated increased 11?-HSD1 levels in skin from older people1 and in sun-exposed compared to sun-protected human skin2. However, the ability of 11?-HSD1 to regulate GC target genes in human skin has not been investigated.

This project aims to investigate 11β-HSD1-mediated regulation of GC target genes in human skin.

You will treat human skin samples with vehicle, cortisone (11β-HSD1 substrate), cortisol (11β-HSD1 product) or cortisone and an 11β-HSD1 inhibitor. GC target gene expression will be measured by quantitative PCR following mRNA extraction and cDNA synthesis. Corresponding changes in protein expression will be confirmed by immunohistochemistry. Using these methods, correlations between 11β-HSD1 and 11β-HSD1-regulated gene expression will also be evaluated in temporal artery biopsies from patients with giant cell arteritis.

References

• Tiganescu, A. et al. Localization, age- and site-dependent expression, and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in skin. J Invest Dermatol. 2011, 131(1), pp.30-6.
• Tiganescu, A. et al. 11beta-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects. J Clin Invest. 2013, 123(7), pp.3051-60.

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