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J Invest Dermatol. 2013 Oct;133(10):2461-2470. doi: 10.1038/jid.2013.164. Epub 2013 Apr 3.

Local arginase 1 activity is required for cutaneous wound healing.

Author information

1
The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, Manchester, UK.
2
Departments of Infectious Diseases and Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
3
Manchester Immunology Group, Faculty of Life Sciences, The University of Manchester, Manchester, UK.
4
The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, Manchester, UK. Electronic address: matthew.j.hardman@manchester.ac.uk.

Abstract

Chronic nonhealing wounds in the elderly population are associated with a prolonged and excessive inflammatory response, which is widely hypothesized to impede healing. Previous studies have linked alterations in local L-arginine metabolism, principally mediated by the enzymes arginase (Arg) and inducible nitric oxide synthase (iNOS), to pathological wound healing. Over subsequent years, interest in Arg/iNOS has focused on the classical versus alternatively activated (M1/M2) macrophage paradigm. Although the role of iNOS during healing has been studied, Arg contribution to healing remains unclear. Here, we report that Arg is dynamically regulated during acute wound healing. Pharmacological inhibition of local Arg activity directly perturbed healing, as did Tie2-cre-mediated deletion of Arg1, revealing the importance of Arg1 during healing. Inhibition or depletion of Arg did not alter alternatively activated macrophage numbers but instead was associated with increased inflammation, including increased influx of iNOS(+) cells and defects in matrix deposition. Finally, we reveal that in preclinical murine models reduced Arg expression directly correlates with delayed healing, and as such may represent an important future therapeutic target.

PMID:
23552798
PMCID:
PMC3778883
DOI:
10.1038/jid.2013.164
[Indexed for MEDLINE]
Free PMC Article
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