Expression of cyclooxygenase 2, microsomal prostaglandin E synthase 1, and EP receptors is increased in rat oesophageal squamous cell dysplasia and Barrett's metaplasia induced by duodenal contents reflux

Abstract

Background and aim: It is known that bile acids can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. A large body of genetic and biochemical evidence indicate that the biosynthetic pathway of prostaglandin E 2 (PGE 2 ) may play an important role in human and rodent tumours. Therefore, we examined the expression pattern of cyclooxygenase 1 (COX-1), COX-2, and microsomal prostaglandin E synthase 1 (mPGES-1), as well as EP receptor subtypes in rat oesophageal lesions induced by duodenal contents reflux. Methods: Oesophagoduodenal anastomosis was performed in rats to induce duodenal contents reflux. We examined histological changes and expression of COX-1, COX-2, mPGES-1, and EP receptor subtypes in the oesophagus by immunohistochemistry and reverse transcription-polymerase chain reaction. Results: Normal control oesophageal tissues showed COX-1 expression in subepithelial stromal cells, including endothelial cells and muscular cells, and did not reveal expression of COX-2 or mPGES-1. In the case of squamous cell lesions, immunoreactivity of COX-1 was similar to that of normal lesions, and COX-2 was maximally expressed around the vascular papillae of tissues showing dysplasia and surrounding epithelial layer and basal layer. mPGES-1 was highly expressed in stromal cells with COX-2 expression. In the case of Barrett's oesophagus, COX-2 and mPGES-1 were predominantly in subepithelial stromal cells. mRNA levels of COX-2, mPGES-1, EP 2 , EP 3 , and EP 4 were higher in the experimental groups than in controls. Conclusions: We suggest that the biosynthetic pathway of PGE 2 may play an important role in oesophageal squamous cell dysplasia and glandular metaplasia induced by duodenal contents reflux.

E Series of Prostaglandin Receptor 2-Mediated Activation of Extracellular Signal-Regulated Kinase/Activator Protein-1 Signaling Is Required for the Mitogenic Action of Prostaglandin E2 in Esophageal Squamous-Cell Carcinoma

“…2, B and D). Up-regulation of EP receptors has been reported in rat Barrett's metaplasia, a premalignant lesion of esophageal adenocarcinoma, induced by duodenal contents reflux (Jang et al, 2004). In this study, we provide direct evidence that the EP2 receptor plays a predominant role in the mediation of the stimulatory effect of PGE 2 in esophageal squamous cell carcinoma.…”

The effects of chronic bile reflux on the gastric mucosa of rats

“…In our model, the squamous epithelium showed significant hyperplasia and papillary bulge, which was also found in the animal models of other studies (27)(28)(29)(30)(31). However, to our knowledge, this is the first study to show the formation of keratin pearls and keratocysts caused by epithelial hyperplasia in an animal model for chronic bile reflux.…”

“…Other studies have found that chronic bile reflux could cause Barrett's esophagus and esophageal adenocarcinoma (27,29,32); however, only 1 case of intestinal metaplasia and no adenocarcinoma occurred for up to 1 year in our rats. This difference in the results may also be attributable to the different operations performed in the studies.…”

Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target

“…This indicates a role for PGE 2 in tumorigenesis (Jabbour et al, 2001;Cohen et al, 2003;Kamei et al, 2003;Jang et al, 2004;Kawata et al, 2006;Shi et al, 2006).…”