Ceramide kinase is required for a normal eicosanoid response and the subsequent orderly migration of fibroblasts.
In these studies, the role of ceramide-1-phosphate (C1P) in the wound-healing process was investigated. Specifically, fibroblasts 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 fibroblasts from CERK(+/+) mice demonstrated steadily increasing levels of arachidonic acid in a time-dependent manner in stark contrast to CERK(-/-) fibroblasts. This observed difference was reflected 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 inflammatory stage to the peak of the fibroplasia stage (e.g., proliferation and migration of fibroblasts). Finally, the loss of proper eicosanoid response translated into an abnormal migration pattern for the fibroblasts isolated from CERK(-/-) As the proper migration of fibroblasts is one of the necessary steps of wound healing, these studies demonstrate a novel requirement for the CERK-derived C1P in the proper healing response of wounds.
Department of Surgery Virginia Commonwealth University-School of Medicine, Richmond, VA 23298 Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, VA 23249.
Dayanjan S
DS
Wijesinghe
Hematology and Medical Oncology, Emory School of Medicine, Atlanta, GA 30322 Miller School of Medicine, University of Miami, Miami, FL 33136.
Matthew
M
Brentnall
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University-School of Medicine, Richmond, VA 23298.
Jennifer A
JA
Mietla
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University-School of Medicine, Richmond, VA 23298.
L Alexis
LA
Hoeferlin
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University-School of Medicine, Richmond, VA 23298.
Robert F
RF
Diegelmann
Hematology and Medical Oncology, Emory School of Medicine, Atlanta, GA 30322.
Lawrence H
LH
Boise
Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, VA 23249 Department of Biochemistry and Molecular Biology, Virginia Commonwealth University-School of Medicine, Richmond, VA 23298 The Massey Cancer Center, Richmond, VA 23298.
Charles E
CE
Chalfant
D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D002518:Ceramides / Q000235:genetics / Q000378:metabolism; D015777:Eicosanoids / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics
D002518:Ceramides; D015777:Eicosanoids; C065576:ceramide 1-phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase
ceramide-1-phosphate; lipidomics; wound healing