Show simple item record

dc.contributor.authorCrompton, Rachel A
dc.contributor.authorWilliams, Helen
dc.contributor.authorCampbell, Laura
dc.contributor.authorLim, Hui Kheng
dc.contributor.authorSaville, Charis
dc.contributor.authorAnsell, David M
dc.contributor.authorReid, Adam
dc.contributor.authorWong, Jason
dc.contributor.authorVardy, Leah A
dc.contributor.authorHardman, Matthew J
dc.contributor.authorCruickshank, Sheena M; email: sheena.cruickshank@manchester.ac.uk
dc.date.accessioned2021-11-11T01:46:23Z
dc.date.available2021-11-11T01:46:23Z
dc.date.issued2021-10-25
dc.date.submitted2021-04-23
dc.identifierpubmed: 34710388
dc.identifierpii: S0022-202X(21)02288-0
dc.identifierdoi: 10.1016/j.jid.2021.09.009
dc.identifier.citationThe Journal of investigative dermatology
dc.identifier.urihttp://hdl.handle.net/10034/626312
dc.descriptionFrom PubMed via Jisc Publications Router
dc.descriptionHistory: received 2021-04-23, revised 2021-09-03, accepted 2021-09-10
dc.descriptionPublication status: aheadofprint
dc.description.abstractNon-healing wounds are a major area of unmet clinical need remaining problematic to treat. Improved understanding of pro-healing mechanisms is invaluable. The enzyme arginase1 is involved in pro-healing responses with its role in macrophages best characterized. Arginase1 is also expressed by keratinocytes; however, arginase1 function in these critical wound repair cells is not understood. We characterized arginase1 expression in keratinocytes during normal cutaneous repair and reveal de novo temporal and spatial expression at the epidermal wound edge. Interestingly, epidermal arginase1 expression was decreased in both human and murine delayed healing wounds. We therefore generated a keratinocyte specific arginase1-null mouse model (K14-cre;Arg1 ) to explore arginase function. Wound repair, linked to changes in keratinocyte proliferation, migration and differentiation, was significantly delayed in K14-cre;Arg1 mice. Similarly, using the arginase inhibitor nor-NOHA, human in vitro and ex vivo models further confirmed this finding, revealing the importance of the downstream polyamine pathway in repair. Indeed, restoring the balance in arginase1 activity via addition of putrescine, proved beneficial in wound closure. In summary, we demonstrate that epidermal arginase1 plays a, to our knowledge, previously unreported intrinsic role in cutaneous healing, highlighting epidermal arginase1 and downstream mediators as potential targets for the therapeutic modulation of wound repair. [Abstract copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.]
dc.languageeng
dc.sourceeissn: 1523-1747
dc.titleAn epidermal-specific role for arginase1 during cutaneous wound repair.
dc.typearticle
dc.date.updated2021-11-11T01:46:23Z
dc.date.accepted2021-09-10


This item appears in the following Collection(s)

Show simple item record