Prosurvival and antiapoptotic effects of PGE2 in radiation injury are mediated by EP2 receptor in intestine.
The biological activities of PGE(2) are mediated through EP receptors (EP(1)-EP(4)), plasma membrane G protein-coupled receptors that differ in ligand binding and signal-transduction pathways. We investigated gastrointestinal EP(2) receptor expression in adult mice before and after radiation injury and evaluated intestinal stem cell survival and crypt epithelial apoptosis after radiation injury in EP(2) null mice. EP(2) was expressed throughout the gut. Intestinal EP(2) mRNA increased fivefold after gamma-irradiation. Crypt survival was diminished in EP(2)-/- mice (4.06 crypts/cross section) compared with wild-type littermates (8.15 crypts/cross section). Radiation-induced apoptosis was significantly increased in EP(2)-/- mice compared with wild-type littermates. Apoptosis was 1.6-fold higher in EP(2) (-/-) mice (5.9 apoptotic cells/crypt) than in wild-type mice (3.5 apoptotic cells/crypt). The EP(2) receptor is expressed in mouse gastrointestinal epithelial cells and is upregulated following radiation injury. The effects of PGE(2) on both crypt epithelial apoptosis and intestinal crypt stem cell survival are mediated through the EP(2) receptor.
Houchen
Courtney W
CW
Department of Medicine, Division of Gastroenterology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. chouchen@im.wustl.edu
Sturmoski
Mark A
MA
Anant
Shrikant
S
Breyer
Richard M
RM
Stenson
William F
WF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015232:Dinoprostone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000473:pathology; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology* / Q000528:radiation effects*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology*; D018078:Receptors, Prostaglandin E / Q000187:drug effects* / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
C545645:Ptger2 protein, mouse; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone