MG53 Mitigates Nitrogen Mustard-Induced Skin Injury
Sulfur mustard (SM) and nitrogen mustard (NM) are vesicant agents that cause skin injury and blistering through complicated cellular events, involving DNA damage, free radical formation, and lipid peroxidation. The development of therapeutic approaches targeting the multi-cellular process of tissue...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/14/1915 |
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| author | Haichang Li Zhongguang Li Xiuchun Li Chuanxi Cai Serena Li Zhao Robert E. Merritt Xinyu Zhou Tao Tan Valerie Bergdall Jianjie Ma |
| author_facet | Haichang Li Zhongguang Li Xiuchun Li Chuanxi Cai Serena Li Zhao Robert E. Merritt Xinyu Zhou Tao Tan Valerie Bergdall Jianjie Ma |
| author_sort | Haichang Li |
| collection | DOAJ |
| description | Sulfur mustard (SM) and nitrogen mustard (NM) are vesicant agents that cause skin injury and blistering through complicated cellular events, involving DNA damage, free radical formation, and lipid peroxidation. The development of therapeutic approaches targeting the multi-cellular process of tissue injury repair can potentially provide effective countermeasures to combat vesicant-induced dermal lesions. MG53 is a vital component of cell membrane repair. Previous studies have demonstrated that topical application of recombinant human MG53 (rhMG53) protein has the potential to promote wound healing. In this study, we further investigate the role of MG53 in NM-induced skin injury. Compared with <i>wild-type</i> mice, <i>mg53<sup>−/−</sup></i> mice are more susceptible to NM-induced dermal injuries, whereas mice with sustained elevation of MG53 in circulation are resistant to dermal exposure of NM. Exposure of keratinocytes and human follicle stem cells to NM causes elevation of oxidative stress and intracellular aggregation of MG53, thus compromising MG53′s intrinsic cell membrane repair function. Topical rhMG53 application mitigates NM-induced dermal injury in mice. Histologic examination reveals the therapeutic benefits of rhMG53 are associated with the preservation of epidermal integrity and hair follicle structure in mice with dermal NM exposure. Overall, these findings identify MG53 as a potential therapeutic agent to mitigate vesicant-induced skin injuries. |
| first_indexed | 2024-03-11T01:11:52Z |
| format | Article |
| id | doaj.art-9baabc4c99314d48a190c0eae4c53a4d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:11:52Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-9baabc4c99314d48a190c0eae4c53a4d2023-11-18T18:46:59ZengMDPI AGCells2073-44092023-07-011214191510.3390/cells12141915MG53 Mitigates Nitrogen Mustard-Induced Skin InjuryHaichang Li0Zhongguang Li1Xiuchun Li2Chuanxi Cai3Serena Li Zhao4Robert E. Merritt5Xinyu Zhou6Tao Tan7Valerie Bergdall8Jianjie Ma9Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery, The Ohio State University, Columbus, OH 43210, USATRIM-Edicine, Inc., 1275 Kinnear Road, Columbus, OH 43212, USADepartment of Veterinary Preventive Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery, The Ohio State University, Columbus, OH 43210, USASulfur mustard (SM) and nitrogen mustard (NM) are vesicant agents that cause skin injury and blistering through complicated cellular events, involving DNA damage, free radical formation, and lipid peroxidation. The development of therapeutic approaches targeting the multi-cellular process of tissue injury repair can potentially provide effective countermeasures to combat vesicant-induced dermal lesions. MG53 is a vital component of cell membrane repair. Previous studies have demonstrated that topical application of recombinant human MG53 (rhMG53) protein has the potential to promote wound healing. In this study, we further investigate the role of MG53 in NM-induced skin injury. Compared with <i>wild-type</i> mice, <i>mg53<sup>−/−</sup></i> mice are more susceptible to NM-induced dermal injuries, whereas mice with sustained elevation of MG53 in circulation are resistant to dermal exposure of NM. Exposure of keratinocytes and human follicle stem cells to NM causes elevation of oxidative stress and intracellular aggregation of MG53, thus compromising MG53′s intrinsic cell membrane repair function. Topical rhMG53 application mitigates NM-induced dermal injury in mice. Histologic examination reveals the therapeutic benefits of rhMG53 are associated with the preservation of epidermal integrity and hair follicle structure in mice with dermal NM exposure. Overall, these findings identify MG53 as a potential therapeutic agent to mitigate vesicant-induced skin injuries.https://www.mdpi.com/2073-4409/12/14/1915alkylating agentsMG53membrane repairdermal healingoxidative stress |
| spellingShingle | Haichang Li Zhongguang Li Xiuchun Li Chuanxi Cai Serena Li Zhao Robert E. Merritt Xinyu Zhou Tao Tan Valerie Bergdall Jianjie Ma MG53 Mitigates Nitrogen Mustard-Induced Skin Injury Cells alkylating agents MG53 membrane repair dermal healing oxidative stress |
| title | MG53 Mitigates Nitrogen Mustard-Induced Skin Injury |
| title_full | MG53 Mitigates Nitrogen Mustard-Induced Skin Injury |
| title_fullStr | MG53 Mitigates Nitrogen Mustard-Induced Skin Injury |
| title_full_unstemmed | MG53 Mitigates Nitrogen Mustard-Induced Skin Injury |
| title_short | MG53 Mitigates Nitrogen Mustard-Induced Skin Injury |
| title_sort | mg53 mitigates nitrogen mustard induced skin injury |
| topic | alkylating agents MG53 membrane repair dermal healing oxidative stress |
| url | https://www.mdpi.com/2073-4409/12/14/1915 |
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