Lysophosphatidic Acid Stimulates Intestinal Restitution via Cytoskeletal Activation and Remodeling

Background. The gastrointestinal tract heals superficial wounds by a process of epithelial migration termed restitution. Restitution is an important response for preventing conditions like stress gastritis, ulcer disease, celiac sprue, ischemia-reperfusion injury, bacterial translocation during shock, and inflammatory bowel disease. The purpose of this study was to determine the effect of a platelet product, lysophosphatidic acid (LPA), on intestinal restitution. Materials and methods. IEC-6 cells were used to study the effect of LPA on intracellular calcium mobilization, actin stress fiber formation, and actin and FAK protein levels. An in vitro model of restitution was utilized to determine the LPA-stimulated IEC-6 migration. Results. LPA administration stimulated intracellular calcium mobilization in a dose-dependent fashion with typical peak and plateau phases suggestive of a receptor-mediated response. Actin stress fiber formation occurred within 15 min after LPA treatment and was especially apparent at 2 h. This response was accompanied by higher actin and FAK protein levels. LPA also stimulated IEC-6 migration 3-fold within 24 h. All of these effects were completely inhibited by pertussis toxin. Conclusions. Exposure of IEC-6 cells to LPA results in significant calcium mobilization and cytoskeletal remodeling within minutes. This activity is accompanied by increased actin and FAK levels. Cellular migration is significantly enhanced by LPA. These responses seem to be due to pertussis-sensitive G-protein-associated receptors. The ability of LPA to potentiate intestinal cell restitution appears, in part, to be mediated by effects on intestinal cell cytoskeletal structure.