Prosurvival and antiapoptotic effects of PGE2 in radiation injury are mediated by EP2 receptor in intestine

Am J Physiol Gastrointest Liver Physiol. 2003 Mar;284(3):G490-8. doi: 10.1152/ajpgi.00240.2002. Epub 2002 Nov 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Blotting, Western
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dinoprostone / pharmacology*
  • Electrophoresis, Polyacrylamide Gel
  • Epithelial Cells / pathology
  • Immunohistochemistry
  • Intestines / pathology*
  • Intestines / radiation effects*
  • Mice
  • RNA, Messenger / biosynthesis
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / pathology*
  • Receptors, Prostaglandin E / drug effects*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype


  • Ptger2 protein, mouse
  • Ptger4 protein, mouse
  • RNA, Messenger
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Dinoprostone