Ceramide kinase is required for a normal eicosanoid response and the subsequent orderly migration of fi broblasts

Abstract

In these studies, the role of ceramide-1-phosphate (C1P) in the wound-healing process was investigated. Specifi cally, fi broblasts isolated from mice with the known anabolic enzyme for C1P, ceramide kinase (CERK), ablated (CERK mice) and their wild-type littermates (CERK +/+ ) were subjected to in vitro wound-healing assays. Simulation of mechanical trauma of a wound by scratching a monolayer of fi broblasts from CERK +/+ mice demonstrated steadily increasing levels of arachidonic acid in a time-dependent manner in stark contrast to CERK fi broblasts. This observed difference was refl ected in scratch-induced eicosanoid levels. Similar, but somewhat less intense, changes were observed in a more complex system utilizing skin biopsies obtained from CERK-null mice. Importantly, C1P levels increased during the early stages of human wound healing correlating with the transition from the infl ammatory stage to the peak of the fi broplasia stage (e.g., proliferation and migration of fi broblasts). Finally, the loss of proper eicosanoid response translated into an abnormal migration pattern for the fi broblasts isolated from CERK. As the proper migration of fi broblasts is one of the necessary steps of wound healing, these studies demonstrate a novel requirement for the CERK-derived C1P in the proper healing. © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.