Expression of protease-activated-receptor 2 (PAR-2) in human esophageal mucosa
Expression of protease-activated-receptor 2 (PAR-2) in human esophageal mucosa
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DOI：
10.1080/00365520902783683
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发表时间：
2009-01-01
影响因子：
1.9
通讯作者：
Casselbrant, Anna
中科院分区：
文献类型：
--
作者：
Inci, Kamuran;Edebo, Anders;Casselbrant, Anna
Objective.十二指肠反流在胃食管反流病（GERD）中的作用仍在讨论中，其中包括胆盐和胰酶（特别注意胰蛋白酶）。蛋白酶激活受体（PARs）是一个新的家族，而PAR-2是该家族中唯一的成员，因为它被胰蛋白酶激活。本研究的目的是检查PAR-2受体的存在和位置的人食管粘膜在不同的亚组GERD。材料和方法。采用逆转录聚合酶链反应（RT-PCR）、蛋白质印迹和免疫组织化学方法对健康对照、糜烂性反流病（ERD）患者、特化肠上皮化生（SIM）患者和腺癌患者的远端活检组织进行PAR-2受体分析。结果PAR-2受体的基因转录本在所有组中均被发现，与对照组相比，SIM患者的水平有所增加。然而，PAR-2受体的蛋白质表达没有观察到这种视觉模式，表明组间没有明显的定量差异。免疫组化显示PAR-2受体在食管上皮的管腔部分的不同染色。结论. PAR-2受体的定位表明，在胃食管反流液中，PAR-2受体可被胰蛋白酶切割和激活。因此，这些数据表明胰蛋白酶-PAR-2通路可能参与GERD的发病机制。
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. Material and 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.