Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 作者机构：
1. The University of Sydney
2. Nanjing University of Chinese Medicine
3. Nottingham Trent University
4. Burns and Reconstructive Surgery Unit, Concord Repatriation General Hospital
- 作者简介：
- 基金信息：
DOI：10.1093/burnst/tkac052
CLC：Published：2023，
Published Online：20 January 2023，
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Kevin H-Y Tsai, Huaikai Shi, Roxanne J Parungao, Sina Naficy, Xiaotong Ding, Xiaofeng Ding, Jonathan J Hew, Xiaosuo Wang, Wojciech Chrzanowski, Gareth G Lavery, Zhe Li, Andrea C Issler-Fisher, Jun Chen, Qian Tan, Peter K Maitz, Mark S Cooper, Yiwei Wang, Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics, Burns & Trauma, Volume 11, 2023, tkac052, https://doi.org/10.1093/burnst/tkac052
Kevin H-Y Tsai, Huaikai Shi, Roxanne J Parungao, Sina Naficy, Xiaotong Ding, Xiaofeng Ding, Jonathan J Hew, Xiaosuo Wang, Wojciech Chrzanowski, Gareth G Lavery, Zhe Li, Andrea C Issler-Fisher, Jun Chen, Qian Tan, Peter K Maitz, Mark S Cooper, Yiwei Wang, Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics, Burns & Trauma, Volume 11, 2023, tkac052, https://doi.org/10.1093/burnst/tkac052 DOI：
摘要
Abstract
BackgroundExcessive scarring and fibrosis are the most severe and common complications of burn injury. Prolonged exposure to high levels of glucocorticoids detrimentally impacts on skin
leading to skin thinning and impaired wound healing. Skin can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). We hypothesised that burn injury would induce 11β-HSD1 expression and local glucocorticoid metabolism
which would have important impacts on wound healing
fibrosis and scarring. We additionally proposed that pharmacological manipulation of this system could improve aspects of post-burn scarring.MethodsSkin 11β-HSD1 expression in burns patients and mice was examined. The impacts of 11β-HSD1 mediating glucocorticoid metabolism on burn wound healing
scar formation and scar elasticity and quality were additionally examined using a murine 11β-HSD1 genetic knockout model. Slow-release scaffolds containing therapeutic agents
including active and inactive glucocorticoids
were developed and pre-clinically tested in mice with burn injury.ResultsWe demonstrate that 11β-HSD1 expression levels increased substantially in both human and mouse skin after burn injury. 11β-HSD1 knockout mice experienced faster wound healing than wild type mice but the healed wounds manifested significantly more collagen deposition
tensile strength and stiffness
features characteristic of excessive scarring. Application of slow-release prednisone
an inactive glucocorticoid
slowed the initial rate of wound closure but significantly reduced post-burn scarring via reductions in inflammation
myofibroblast generation
collagen production and scar stiffness.ConclusionsSkin 11β-HSD1 expression is a key regulator of wound healing and scarring after burn injury. Application of an inactive glucocorticoid capable of activation by local 11β-HSD1 in skin slows the initial rate of wound closure but significantlyimproves scar characteristics post burn injury.
关键词
Keywords
Wound healingBurn injuryScarringSkin 11β-HSD111β-HSD1 knockoutGlucocorticoid metabolismPolycaprolactone scaffoldDrug delivery
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