Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice

Androgens have been known to inhibit cutaneous wound healing in men and male mice. However, in children with major burn injuries, a synthetic androgen was reported clinically to improve wound healing. The aim of this study is to investigate the role of dihydrotestosterone (DHT) as a new therapeutic...

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Main Authors: Huaikai Shi, Tsun-Ho Lo, Duncan Ma, Brenton Condor, Brian Lesmana, Roxanne J Parungao, Kevin H.-Y. Tsai, Sarah Kim, Hsiao-Ting Chen, Pablo A Silveira, Zhe Li, Mark S Cooper, Ulla Simanainen, David J Handelsman, Peter K Maitz, Yiwei Wang
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/17/6231
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author Huaikai Shi
Tsun-Ho Lo
Duncan Ma
Brenton Condor
Brian Lesmana
Roxanne J Parungao
Kevin H.-Y. Tsai
Sarah Kim
Hsiao-Ting Chen
Pablo A Silveira
Zhe Li
Mark S Cooper
Ulla Simanainen
David J Handelsman
Peter K Maitz
Yiwei Wang
author_facet Huaikai Shi
Tsun-Ho Lo
Duncan Ma
Brenton Condor
Brian Lesmana
Roxanne J Parungao
Kevin H.-Y. Tsai
Sarah Kim
Hsiao-Ting Chen
Pablo A Silveira
Zhe Li
Mark S Cooper
Ulla Simanainen
David J Handelsman
Peter K Maitz
Yiwei Wang
author_sort Huaikai Shi
collection DOAJ
description Androgens have been known to inhibit cutaneous wound healing in men and male mice. However, in children with major burn injuries, a synthetic androgen was reported clinically to improve wound healing. The aim of this study is to investigate the role of dihydrotestosterone (DHT) as a new therapeutic approach in treating major burn injury. In the present study, mice received systemic androgen treatment post major burn injury. Wound healing rate and body weight were monitored over 21 days. The serum level of inflammatory cytokines/chemokines were measured using multiplex immunoassays. In addition, splenocyte enumeration was performed by flow cytometry. Healing phases of inflammation, re-epithelialization, cell proliferation and collagen deposition were also examined. In results, DHT treated mice lost less weight and displayed accelerated wound healing but has no impact on hypermetabolism. Mice, after burn injury, displayed acute systemic inflammatory responses over 21 days. DHT treatment shortened the systemic inflammatory response with reduced splenic weight and monocyte numbers on day 14 and 21. DHT treatment also reduced wound infiltrating macrophage numbers. In conclusion, DHT treatment facilitates local wound healing by accelerating the resolution of inflammation, but not through alterations of post-burn hypermetabolic response.
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spelling doaj.art-0767d5f2577d4a58a3a7585957837a1f2023-11-20T11:43:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117623110.3390/ijms21176231Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in MiceHuaikai Shi0Tsun-Ho Lo1Duncan Ma2Brenton Condor3Brian Lesmana4Roxanne J Parungao5Kevin H.-Y. Tsai6Sarah Kim7Hsiao-Ting Chen8Pablo A Silveira9Zhe Li10Mark S Cooper11Ulla Simanainen12David J Handelsman13Peter K Maitz14Yiwei Wang15Burns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaDendritic Cell Research, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBurns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBurns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBurns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBurns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaAdrenal Steroids Laboratory, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBone Biology Group, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaDendritic Cell Research, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaDendritic Cell Research, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBurns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaAdrenal Steroids Laboratory, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaAndrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaAndrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBurns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaBurns Research and Reconstructive Surgery, ANZAC Research Institute, University of Sydney, Sydney 2139, AustraliaAndrogens have been known to inhibit cutaneous wound healing in men and male mice. However, in children with major burn injuries, a synthetic androgen was reported clinically to improve wound healing. The aim of this study is to investigate the role of dihydrotestosterone (DHT) as a new therapeutic approach in treating major burn injury. In the present study, mice received systemic androgen treatment post major burn injury. Wound healing rate and body weight were monitored over 21 days. The serum level of inflammatory cytokines/chemokines were measured using multiplex immunoassays. In addition, splenocyte enumeration was performed by flow cytometry. Healing phases of inflammation, re-epithelialization, cell proliferation and collagen deposition were also examined. In results, DHT treated mice lost less weight and displayed accelerated wound healing but has no impact on hypermetabolism. Mice, after burn injury, displayed acute systemic inflammatory responses over 21 days. DHT treatment shortened the systemic inflammatory response with reduced splenic weight and monocyte numbers on day 14 and 21. DHT treatment also reduced wound infiltrating macrophage numbers. In conclusion, DHT treatment facilitates local wound healing by accelerating the resolution of inflammation, but not through alterations of post-burn hypermetabolic response.https://www.mdpi.com/1422-0067/21/17/6231major burn injuryandrogensdihydrotestosteronewound healinginflammationmouse model
spellingShingle Huaikai Shi
Tsun-Ho Lo
Duncan Ma
Brenton Condor
Brian Lesmana
Roxanne J Parungao
Kevin H.-Y. Tsai
Sarah Kim
Hsiao-Ting Chen
Pablo A Silveira
Zhe Li
Mark S Cooper
Ulla Simanainen
David J Handelsman
Peter K Maitz
Yiwei Wang
Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice
International Journal of Molecular Sciences
major burn injury
androgens
dihydrotestosterone
wound healing
inflammation
mouse model
title Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice
title_full Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice
title_fullStr Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice
title_full_unstemmed Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice
title_short Dihydrotestosterone (DHT) Enhances Wound Healing of Major Burn Injury by Accelerating Resolution of Inflammation in Mice
title_sort dihydrotestosterone dht enhances wound healing of major burn injury by accelerating resolution of inflammation in mice
topic major burn injury
androgens
dihydrotestosterone
wound healing
inflammation
mouse model
url https://www.mdpi.com/1422-0067/21/17/6231
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