Prostaglandins and epithelial response to injury

Purpose of review This review will highlight recent studies in the role of prostaglandins in regulating the epithelial response to injury in the gastrointestinal tract. Recent findings Prostaglandins, particularly PGE(2), regulate intestinal epithelial apoptosis and proliferation in the face of injury. In the dextran sodium sulphate colitis model, PGE(2), produced through cyclooxygenase-2, supports epithelial proliferation. Two studies demonstrated that PGE(2) is an important Mediator of the protective effects of toll-like receptor signaling in the dextran sulphate sodium model. One study suggested that toll-like receptor signaling induced cyclooxygenase-2 expression whereas the other suggested that toll-like receptor signaling induces the repositioning of cyclooxygenase-2 expressing stromal cells. PGE(2) is also protective of small intestinal epithelial cells in the radiation injury model. In this model PGE(2) decreases radiation-induced apoptosis and increases crypt survival. PGE(2) binds to EP receptors; EP2 appears to be especially important in mediating the protective effects of PGE(2) on epithelial cells. The intracellular signaling pathways by which PGE(2) mediates its pro-proliferative and antiapoptotic effects include the PI3 kinase/Akt pathway, the MAP kinase pathway and the P-catenin pathway. Summary Endogenous PGE(2) has pro-proliferative and antiapoptotic effects on epithelial cells in gastrointestinal injury.