title: Involvement of the CXCL12/CXCR4 pathway in the recovery of skin following burns.
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.
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Avniel
authors.forename: Zaretski
authors.initials: Z
authors.lastname: Arik
authors.forename: Alex
authors.initials: A
authors.lastname: Maly
authors.forename: Assa
authors.initials: A
authors.lastname: Sagie
authors.forename: Hanna Ben
authors.initials: HB
authors.lastname: Basst
authors.forename: Merav Darash
authors.initials: MD
authors.lastname: Yahana
authors.forename: Ido D
authors.initials: ID
authors.lastname: Weiss
authors.forename: Boaz
authors.initials: B
authors.lastname: Pal
authors.forename: Ori
authors.initials: O
authors.lastname: Wald
authors.forename: Dean
authors.initials: D
authors.lastname: Ad-El
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.forename: Eyal
authors.initials: E
authors.lastname: Gur
authors.forename: Amnon
authors.initials: A
authors.lastname: Peled
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002056:Burns / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects; D012867:Skin / Q000737:chemistry / Q000293:injuries* / Q000473:pathology; D012879:Skin Physiological Phenomena; D013552:Swine
chemical_list: C477728:4-fluorobenzoyl-TN-14003; D000906:Antibodies; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D010455:Peptides; D019718:Receptors, CXCR4; D009569:Nitric Oxide