Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing
Arginase (ARG) represents an important evolutionarily conserved enzyme that is expressed by multiple cell types in the skin. Arg acts as the mediator of the last step of the urea cycle, thus providing protection against excessive ammonia under homeostatic conditions through the production of L-ornit...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.773866/full |
| _version_ | 1819005325044350976 |
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| author | Denis C. Szondi Jason K. Wong Leah A. Vardy Sheena M. Cruickshank |
| author_facet | Denis C. Szondi Jason K. Wong Leah A. Vardy Sheena M. Cruickshank |
| author_sort | Denis C. Szondi |
| collection | DOAJ |
| description | Arginase (ARG) represents an important evolutionarily conserved enzyme that is expressed by multiple cell types in the skin. Arg acts as the mediator of the last step of the urea cycle, thus providing protection against excessive ammonia under homeostatic conditions through the production of L-ornithine and urea. L-ornithine represents the intersection point between the ARG-dependent pathways and the urea cycle, therefore contributing to cell detoxification, proliferation and collagen production. The ARG pathways help balance pro- and anti-inflammatory responses in the context of wound healing. However, local and systemic dysfunctionalities of the ARG pathways have been shown to contribute to the hindrance of the healing process and the occurrence of chronic wounds. This review discusses the functions of ARG in macrophages and fibroblasts while detailing the deleterious implications of a malfunctioning ARG enzyme in chronic skin conditions such as leg ulcers. The review also highlights how ARG links with the microbiota and how this impacts on infected chronic wounds. Lastly, the review depicts chronic wound treatments targeting the ARG pathway, alongside future diagnosis and treatment perspectives. |
| first_indexed | 2024-12-20T23:50:59Z |
| format | Article |
| id | doaj.art-bc8ecb0ebe684e58a0a88248184d6e9c |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-20T23:50:59Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-bc8ecb0ebe684e58a0a88248184d6e9c2022-12-21T19:22:50ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-10-01810.3389/fmolb.2021.773866773866Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and HealingDenis C. Szondi0Jason K. Wong1Leah A. Vardy2Sheena M. Cruickshank3Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomBlond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomSkin Research Institute of Singapore, A*STAR, Singapore, SingaporeLydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomArginase (ARG) represents an important evolutionarily conserved enzyme that is expressed by multiple cell types in the skin. Arg acts as the mediator of the last step of the urea cycle, thus providing protection against excessive ammonia under homeostatic conditions through the production of L-ornithine and urea. L-ornithine represents the intersection point between the ARG-dependent pathways and the urea cycle, therefore contributing to cell detoxification, proliferation and collagen production. The ARG pathways help balance pro- and anti-inflammatory responses in the context of wound healing. However, local and systemic dysfunctionalities of the ARG pathways have been shown to contribute to the hindrance of the healing process and the occurrence of chronic wounds. This review discusses the functions of ARG in macrophages and fibroblasts while detailing the deleterious implications of a malfunctioning ARG enzyme in chronic skin conditions such as leg ulcers. The review also highlights how ARG links with the microbiota and how this impacts on infected chronic wounds. Lastly, the review depicts chronic wound treatments targeting the ARG pathway, alongside future diagnosis and treatment perspectives.https://www.frontiersin.org/articles/10.3389/fmolb.2021.773866/fullwound healingarginase (ARG)chronic woundspolyaminesdiabetic foot ulcers (DFU)venous leg ulcers (VLU) |
| spellingShingle | Denis C. Szondi Jason K. Wong Leah A. Vardy Sheena M. Cruickshank Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing Frontiers in Molecular Biosciences wound healing arginase (ARG) chronic wounds polyamines diabetic foot ulcers (DFU) venous leg ulcers (VLU) |
| title | Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing |
| title_full | Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing |
| title_fullStr | Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing |
| title_full_unstemmed | Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing |
| title_short | Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing |
| title_sort | arginase signalling as a key player in chronic wound pathophysiology and healing |
| topic | wound healing arginase (ARG) chronic wounds polyamines diabetic foot ulcers (DFU) venous leg ulcers (VLU) |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.773866/full |
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