Involvement of the CXCL12/CXCR4 pathway in the recovery of skin following burns

Shani Avniel, Zaretski Arik, Alex Maly, Assa Sagie, Hanna Ben Basst, Merav Darash Yahana, Ido D. Weiss, Boaz Pal, Ori Wald, Dean Ad-El, Nobutaka Fujii, Fernando Arenzana-Seisdedos, Steffen Jung, Eithan Galun, Eyal Gur*, Amnon Peled

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Burn wound healing is a complex process consisting of an inflammatory phase, the formation of granulation tissue, and remodeling. The role of the CXCL12/CXCR4 pathway in the recovery of skin following burns is unknown. We found that CXCL12 is similarly expressed in human, swine, and rat skin by pericyte and endothelial cells, fibrous sheet, fibroblasts, and axons. Following burns, the levels of CXCL12 were markedly increased in human burn blister fluids. One day after injury, there was a gradual increase in the expression of CXCL12 in the hair follicles and in blood vessel endothelium surrounding the burn. Three to 11 days following burns, an increased number of fibroblasts expressing CXCL12 were observed in the recovering dermis of rat, swine, and human skin. In contrast to CXCL12, CXCR4 expression was detected in proliferating epithelial cells as well as in eosinophils and mononuclear cells infiltrating the skin. In vitro, CXCL12 was expressed by primary human skin fibroblasts, but not by keratinocytes, and was stimulated by wounding a confluent cell layer of these fibroblasts. Blocking the CXCR4/CXCL12 axis resulted in the significant reduction in eosinophil accumulation in the dermis and improved epithelialization. Thus, blocking CXCR4/CXCL12 interaction may significantly improve skin recovery after burns.

Original languageAmerican English
Pages (from-to)468-476
Number of pages9
JournalJournal of Investigative Dermatology
Volume126
Issue number2
DOIs
StatePublished - Feb 2006

Bibliographical note

Funding Information:
We thank Mery Clausen (Gene Therapy Institute, Hadassah Hospital) for technical assistance. This study was supported by the Horwitz Foundation, the Israeli Ministry of Science – the Knowledge Center for Gene Therapy, the Blum Foundation, and the Grinspoon Foundation.

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