Prostaglandins and epithelial response to injury.
OBJECTIVE
This review will highlight recent studies in the role of prostaglandins in regulating the epithelial response to injury in the gastrointestinal tract.


RESULTS
Prostaglandins, particularly PGE2, regulate intestinal epithelial apoptosis and proliferation in the face of injury. In the dextran sodium sulphate colitis model, PGE2, produced through cyclooxygenase-2, supports epithelial proliferation. Two studies demonstrated that PGE2 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. PGE2 is also protective of small intestinal epithelial cells in the radiation injury model. In this model PGE2 decreases radiation-induced apoptosis and increases crypt survival. PGE2 binds to EP receptors; EP2 appears to be especially important in mediating the protective effects of PGE2 on epithelial cells. The intracellular signaling pathways by which PGE2 mediates its pro-proliferative and antiapoptotic effects include the PI3 kinase/Akt pathway, the MAP kinase pathway and the beta-catenin pathway.


CONCLUSIONS
Endogenous PGE2 has pro-proliferative and antiapoptotic effects on epithelial cells in gastrointestinal injury.
Stenson
William F
WF
Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. WStenson@im.wustl.edu
D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000139:chemically induced; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000528:radiation effects; D011453:Prostaglandins / Q000378:metabolism*; D011832:Radiation Injuries / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism
D011453:Prostaglandins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051546:Cyclooxygenase 2; D015232:Dinoprostone