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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.