| First Author | Tiganescu A | Year | 2018 |
| Journal | Endocrinology | Volume | 159 |
| Issue | 1 | Pages | 547-556 |
| PubMed ID | 29087473 | Mgi Jnum | J:256400 |
| Mgi Id | MGI:6108060 | Doi | 10.1210/en.2017-00607 |
| Citation | Tiganescu A, et al. (2018) Topical 11beta-Hydroxysteroid Dehydrogenase Type 1 Inhibition Corrects Cutaneous Features of Systemic Glucocorticoid Excess in Female Mice. Endocrinology 159(1):547-556 |
| abstractText | Glucocorticoid (GC) excess drives multiple cutaneous adverse effects, including skin thinning and poor wound healing. The ubiquitously expressed enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activates mouse corticosterone from 11-dehydrocorticosterone (and human cortisol from cortisone). We previously demonstrated elevated 11beta-HSD1 activity during mouse wound healing, but the interplay between cutaneous 11beta-HSD1 and systemic GC excess is unexplored. Here, we examined effects of 11beta-HSD1 inhibition by carbenoxolone (CBX) in mice treated with corticosterone (CORT) or vehicle for 6 weeks. Mice were treated bidaily with topical CBX or vehicle (VEH) 7 days before wounding and during wound healing. CORT mice displayed skin thinning and impaired wound healing but also increased epidermal integrity. 11beta-HSD1 activity was elevated in unwounded CORT skin and was inhibited by CBX. CORT mice treated with CBX displayed 51%, 59%, and 100% normalization of wound healing, epidermal thickness, and epidermal integrity, respectively. Gene expression studies revealed normalization of interleukin 6, keratinocyte growth factor, collagen 1, collagen 3, matrix metalloproteinase 9, and tissue inhibitor of matrix metalloproteinase 4 by CBX during wound healing. Importantly, proinflammatory cytokine expression and resolution of inflammation were unaffected by 11beta-HSD1 inhibition. CBX did not regulate skin function or wound healing in the absence of CORT. Our findings demonstrate that 11beta-HSD1 inhibition can limit the cutaneous effects of GC excess, which may improve the safety profile of systemic steroids and the prognosis of chronic wounds. |
