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
- 1Department of Pathology, Dongguk University College of Medicine, Kyongju, Korea
- 2Department of General Surgery, College of Medicine Ewha Womans University, Seoul, Korea
- 3Department of General Surgery, Dongguk University College of Medicine, Kyongju, Korea
- Correspondence to:
Professor T J Jang
Department of Pathology, Dongguk University, College of Medicine, 707 Suekjang-dong, Kyongju, Kyongbuk 780-714, Korea;
- Accepted 11 August 2003
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 E2 (PGE2) 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, EP2, EP3, and EP4 were higher in the experimental groups than in controls.
Conclusions: We suggest that the biosynthetic pathway of PGE2 may play an important role in oesophageal squamous cell dysplasia and glandular metaplasia induced by duodenal contents reflux.
- cyclooxygenase 2
- microsomal prostaglandin E synthase 1
- EP receptors
- squamous cell dysplasia
- Barrett’s oesophagus
- COX, cyclooxygenase
- mPGES-1, microsomal prostaglandin E synthase 1
- PG, prostaglandin
- BrdU, bromodeoxyuridine
- RT-PCR, reverse transcription-polymerase chain reaction
- GAPDH, glyceraldehyde 3-phosphate dehydrogenase
- VEGF, vascular endothelial growth factor
- HIF-1α, hypoxia inducible factor 1α
- NSAIDs, non-steroidal anti-inflammatory drugs