Expression of protease-activated-receptor 2 (PAR-2) in human esophageal mucosa.
OBJECTIVE
The role of duodenal reflux in gastroesophageal reflux disease (GERD) containing bile salts and pancreatic enzymes (with special attention to trypsin) is still under discussion. Proteinase-activated receptors (PARs) are a novel family and PAR-2 is a unique member of this family because it is activated by trypsin. The aim of the present study was to examine the presence and the position of the PAR-2 receptor in human esophageal mucosa in different subgroups of GERD.


METHODS
Distal biopsies taken from healthy controls, patients with erosive reflux disease (ERD), patients with specialized intestinal metaplasia (SIM) and adenocarcinoma were analyzed for the PAR-2 receptor with reverse-transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry.


RESULTS
Gene transcripts for the PAR-2 receptor were found in all groups, with increased levels in SIM patients compared to controls. However, this visual pattern was not seen for the protein expression of the PAR-2 receptor showing no apparent quantitative differences between the groups. Immunohistochemistry revealed distinct staining for the PAR-2 receptor in the luminal part of the esophageal epithelium.


CONCLUSIONS
The localization of the PAR-2 receptor indicates that the receptor can be cleaved and activated by trypsin in duodenogastric esophageal refluxate. The data thus suggest that the trypsin-PAR-2 pathway may be involved in the pathogenesis of GERD.
Inci
Kamuran
K
Department of Gastrosurgical Research and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Edebo
Anders
A
Olbe
Lars
L
Casselbrant
Anna
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology; D044464:Receptor, PAR-2 / Q000096:biosynthesis*
D044464:Receptor, PAR-2