TY - JOUR
T1 - Involvement of the CXCL12/CXCR4 pathway in the recovery of skin following burns
AU - Avniel, Shani
AU - Arik, Zaretski
AU - Maly, Alex
AU - Sagie, Assa
AU - Basst, Hanna Ben
AU - Yahana, Merav Darash
AU - Weiss, Ido D.
AU - Pal, Boaz
AU - Wald, Ori
AU - Ad-El, Dean
AU - Fujii, Nobutaka
AU - Arenzana-Seisdedos, Fernando
AU - Jung, Steffen
AU - Galun, Eithan
AU - Gur, Eyal
AU - Peled, Amnon
N1 - 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.
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33644640532&partnerID=8YFLogxK
U2 - 10.1038/sj.jid.5700069
DO - 10.1038/sj.jid.5700069
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C2 - 16385346
AN - SCOPUS:33644640532
SN - 0022-202X
VL - 126
SP - 468
EP - 476
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -