Migration inhibitory factor-related protein (MRP)8 and MRP14 are differentially expressed in free-electron laser and scalpel incisions.
Incisions made in mouse skin by scalpel or the free-electron laser heal at different rates. To identify genes that are differentially expressed in free-electron laser or scalpel wounds, we isolated total RNA from free-electron laser- or scalpel-produced incisions and normal skin at day 7 postwounding. cDNA microarray analysis identified 89 of 15,000 genes in a mouse microarray as having significantly different expression levels. Migration inhibitory factor-related protein (MRP) 14 was almost 30 times more highly expressed in scalpel wounds than in free-electron laser wounds. This result was confirmed by Northern blot analysis, which also showed that scalpel wounds expressed higher levels of MRP8, a related S100 protein that can heterodimerize with MRP14, at days 2, 7, and 14 postwounding. Free-electron laser wounds also showed elevated expression of MRP8 and MRP14 relative to normal skin. In situ hybridization showed that the patterns of MRP14 and MRP8 expression in free-electron laser and scalpel wound tissues were similar. MRP14 and MRP8 were expressed in the dermal wound margin, while a very low level of MRP14 and MRP8 expression was seen in the migrating epidermis. Dual immunofluorescence staining for MRP14 or MRP8 and macrophage (F4/80) showed that most of the wound macrophages simultaneously expressed MRP14 and MRP8. Some expression was also found in neutrophils, while neither antigen accumulated to a significant degree in the epidermis. Relatively lower MRP8 and 14 expression in free-electron laser wounds was correlated with a higher level of matrix metalloproteinase-13 expression and a reduced rate of wound healing. While the regulation of MRP8 expression in mouse may be different from human skin, we suggest that elevated expression of MRP8 and MRP14 may have a relevant therapeutic effect against inflammation in wound healing.
Wu
Nanjun
N
Department of Pathology, Vanderbilt University School of Medicine, Medical Center, Nashville, TN 37232-2561, USA.
Davidson
Jeffrey M
JM
D000818:Animals; D040501:Calgranulin A / Q000276:immunology*; D040502:Calgranulin B / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D053685:Laser Therapy; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000293:injuries*; D013514:Surgical Procedures, Operative; D014945:Wound Healing / Q000276:immunology*
D040501:Calgranulin A; D040502:Calgranulin B; D008263:Macrophage Migration-Inhibitory Factors