The effect of AgK114 on wound healing.

AgK114 is a newly isolated membrane-associated protein which is expressed on keratinocytes. Its expression is restricted to dermal sheath cells near sebaceous glands in normal skin. However, it is transiently induced by UV exposure or injury stimulation (Tatefuji T. et al., Biol. Pharm. Bull., 27, 1742-1749, 2004). Thus, the expression pattern of AgK114 suggested its potential role in wound healing response. We report here that expression of AgK114 is induced in the initial 24 h at the edge keratinocytes during keratinocyte migration, followed by disappearance once epithelialization is completed in the murine excisional wound model. We also demonstrate that exogenous recombinant mouse AgK114FL promoted wound healing process. Mouse AgK114FL up-regulated pro-matrix-metalloproteinase-9, vascular endothelial growth factor, transforming growth factor-beta, IL-6, and IL-1beta production in the early stage of wound tissue. Moreover, mouse AgK114FL induced the matrix-metalloproteinase-9 activity of wound fibroblasts prepared from impaired skin in the presence of proinflammatory cytokines. These results suggest that the AgK114 participates in the wound response during the healing process, and promotes wound repair.