Hypothesis: Ephrin-Eph Signaling Pathways Provide Novel Targets for Accelerated Re-Epithelialization of Cutaneous...

Cutaneous wound repair is tightly regulated by numerous signaling pathways that coordinate a multiphased response. The repair process includes a proliferative phase that forms granulation tissue at the wound base and re-epithelialization of the wound surface. Two of the signaling pathways that regulate the proliferative phase are Wnt/β-catenin and Notch, stimulating the proliferation of keratinocytes and fibroblasts, respectively. While ephrin-Eph signaling pathways also induce keratinocyte proliferation, their contribution to cutaneous wound repair is less defined. In distal limb wounds on horses, the proliferative phase is often characterized by the formation of excessive granulation tissue that delays healing by impeding keratinocyte migration from the wound margin. Comparison of normal and aberrant healing makes distal limb horse wounds well-suited for defining molecular mechanisms that regulate repair during the proliferative phase and identifying targets that promote healthy wound healing. We hypothesize that ephrin-Eph signaling pathways that stimulate keratinocyte proliferation provide an unexplored but effective target for accelerating re-epithelialization in distal limb wounds of the horse. As re-epithelialization is a key to physiologic healing in many mammals, we further hypothesize that ephrin-Eph signaling pathways offer targets for enhanced wound repair in humans.