Inci Kamuran, Edebo Anders, Olbe Lars, Casselbrant Anna
Department of Gastrosurgical Research and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Scand J Gastroenterol. 2009;44(6):664-71. doi: 10.1080/00365520902783683.
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.
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.
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.
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.
十二指肠反流在含有胆盐和胰酶（尤其关注胰蛋白酶）的胃食管反流病（GERD）中的作用仍在讨论中。蛋白酶激活受体（PARs）是一个新的家族，PAR-2是该家族的一个独特成员，因为它可被胰蛋白酶激活。本研究的目的是检测GERD不同亚组患者食管黏膜中PAR-2受体的存在情况及定位。
采用逆转录聚合酶链反应（RT-PCR）、蛋白质印迹法和免疫组织化学法，对取自健康对照者、糜烂性反流病（ERD）患者、特殊肠化生（SIM）患者及腺癌患者的远端活检组织进行PAR-2受体分析。
所有组均发现PAR-2受体的基因转录本，与对照组相比，SIM患者的水平升高。然而，PAR-2受体的蛋白表达未呈现出这种直观模式，各组之间未显示出明显的定量差异。免疫组织化学显示食管上皮腔面部分的PAR-2受体有明显染色。
PAR-2受体的定位表明该受体可被十二指肠胃食管反流物中的胰蛋白酶切割并激活。因此，数据提示胰蛋白酶-PAR-2途径可能参与GERD的发病机制。
