A lipidomics approach towards understanding eicosanoid signaling events and the role of ceramide kinase during the wound healing process

A complex ballet of eicosanoids plays a crucial role in the onset and resolution of the inflammation stage of wound healing. The Group IV Phospholipase A2 (cPLA 2 α) liberates arachidonic acid from the Sn‐2 position of glycerophospholipids and thereby regulates the initial rate determining step of eicosanoid synthesis. Our laboratory was the first to demonstrate that ceramide‐1‐phosphate, is an activator of cPLA 2 α. Fibroblasts are one of the first cells to respond to wounding via the induction of a robust eicosanoid response. In order to investigate the role of CERK‐derived C1P in the wound healing process, fibroblasts isolated from wild type and CERK knockout mouse embryos were subjected to in vitro wound healing assays. Simulation of a wound by scratching a monolayer of cells (mechanical trauma) demonstrated steadily increasing levels of AA over a 4 hour period while the AA levels from the CERK−/− were unchanged. This difference was reflected in the scratch‐induced eicosanoid levels with PGE2, PGD2, PGF2α, and the HETES all demonstrating significantly reduced eicosanoid response compared to wild type levels. In addition, the embryonic fibroblasts isolated from CERK −/− mice were deficient in migration to a scratched area, which is linked in the literature to eicosanoids. Thus, for the first time, a link between CERK‐derived C1P and the synthesis of eicosanoids in wound healing responses has been identified.