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

被引:58
作者
Houchen, CW
Sturmoski, MA
Anant, S
Breyer, RM
Stenson, WF
机构
[1] Washington Univ, Sch Med, Dept Med, Div Gastroenterol, St Louis, MO 63110 USA
[2] Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37232 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2003年 / 284卷 / 03期
关键词
prostaglandin; cyclooxygenase; prostaglandins; receptor signaling;
D O I
10.1152/ajpgi.00240.2002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The biological activities of PGE(2) are mediated through EP receptors (EP1-EP4), plasma membrane G protein- coupled receptors that differ in ligand binding and signal-transduction pathways. We investigated gastrointestinal EP2 receptor expression in adult mice before and after radiation injury and evaluated intestinal stem cell survival and crypt epithelial apoptosis after radiation injury in EP2 null mice. EP2 was expressed throughout the gut. Intestinal EP2 mRNA increased fivefold after gamma-irradiation. Crypt survival was diminished in EP2-/- mice (4.06 crypts/cross section) compared with wild-type littermates (8.15 crypts/cross section). Radiation-induced apoptosis was significantly increased in EP2-/- mice compared with wild-type littermates. Apoptosis was 1.6-fold higher in EP2-/- mice (5.9 apoptotic cells/crypt) than in wild-type mice (3.5 apoptotic cells/crypt). The EP2 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 EP2 receptor.
引用
收藏
页码:G490 / G498
页数:9
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