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Elevated local senescence in diabetic wound healing is linked to pathological repair via CXCR2.

Wilkinson, Holly N.; Clowes, Christopher; Banyard, Kayleigh L.; Matteuci, Paolo; Mace, Kimberly; Hardman, Matthew J.

Authors

Christopher Clowes

Kayleigh L. Banyard

Paolo Matteuci

Kimberly Mace



Abstract

Cellular senescence can be broadly defined as a stable, yet essentially irreversible, loss of proliferative capacity. Historically, senescence is described as a negative outcome of advanced cellular age. It is now clear, however, that senescence represents a dynamic autonomous stress response, integral to long-term tumour suppression. Intriguingly, transient induction of a senescent phenotype has actually been suggested to promote regeneration in both liver and skin. Here we explored the role of senescence in pathological aged and diabetic murine wound healing. Aged and diabetic wounds possessed greater numbers of senescent cells, while diabetic macrophages maintained altered retention of polarisation and produced a CXCR2-enriched SASP. Of translational relevance, targeted expression of CXCR2 in primary human dermal fibroblasts led to paracrine induction of nuclear p21. Further, a selective agonist to CXCR2 was able to reverse delayed healing in diabetic mice and accelerate ex vivo human skin wound healing. Collectively these data suggest a hitherto unappreciated role for CXCR2 in mediating cellular senescence in pathological wound repair.

Citation

Wilkinson, H. N., Clowes, C., Banyard, K. L., Matteuci, P., Mace, K., & Hardman, M. J. (2019). Elevated local senescence in diabetic wound healing is linked to pathological repair via CXCR2. Journal of Investigative Dermatology, 139(5), 1171-1181.e6. https://doi.org/10.1016/j.jid.2019.01.005

Journal Article Type Article
Acceptance Date Jan 8, 2019
Online Publication Date Jan 23, 2019
Publication Date 2019-05
Deposit Date Jan 30, 2019
Publicly Available Date Jul 24, 2019
Journal Journal of Investigative Dermatology
Print ISSN 0022-202x
Electronic ISSN 1523-1747
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 139
Issue 5
Pages 1171-1181.e6
DOI https://doi.org/10.1016/j.jid.2019.01.005
Keywords Senescence; Wound healing; Ageing; Diabetes; Macrophage polarisation
Public URL https://hull-repository.worktribe.com/output/1250509
Publisher URL https://www.sciencedirect.com/science/article/pii/S0022202X19300211?via%3Dihub#kwrds0010
Additional Information This is the accepted manuscript of an article published in Journal of investigative dermatology, 2019. The version of record is available at the DOI link in this record.

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