Dataset Information

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.

ABSTRACT: Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein-coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3?, MIG, RANTES and interleukin (IL)-1? as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.org.

SUBMITTER: Abdel-Aziz H

PROVIDER: S-EPMC4982478 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.

Abdel-Aziz Heba H Schneider Mathias M Neuhuber Winfried W Meguid Kassem Abdel A Khailah Saleem S Müller Jürgen J Gamal Eldeen Hadeel H Khairy Ahmed A T Khayyal Mohamed M Shcherbakova Anastasiia A Efferth Thomas T Efferth Thomas T Ulrich-Merzenich Gudrun G

Molecular medicine (Cambridge, Mass.) 20160509 1

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic refl ...[more]

PMID: 26650186

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Project description:Background and study aims ?Non-erosive reflux disease (NERD) includes minimal change esophagitis (MCE) and no endoscopic abnormalities. However, for most endoscopists, it is difficult to detect MCE with conventional white-light endoscopy (WLE). Linked color imaging (LCI) technology is the most recently developed image-enhancing technology and improves detection and differentiation of subtle mucosal changes using a color contrast method. This study assessed the efficacy of WLE combined with LCI for diagnosing MCE compared with WLE. Patients and methods ?Between February and May 2017, 44 NERD patients and 40 healthy subjects were enrolled in our study. First, the distal esophagus was examined using WLE followed by LCI. Second, three experienced endoscopists observed all the patients' white-light (WL) images and corresponding images of WL and LCI and then recorded presence or absence of minimal change esophagitis (MCE?+/-). The proportion of minimal change between the two groups was then compared. Third, five blinded endoscopists with different levels of endoscopic experience assessed whether MCE was present. Intraobserver reproducibility and interobserver agreement were described using the kappa value. Results ?The proportion of MCE in the NERD group (70.8?%, 35/48) was higher than that in the control group (22.5?%, 9/40, P ?<?0.001) when diagnosed by the three experienced endoscopists. Detection rates for MCE using WLE combined with LCI were higher than those using WLE (43/88, 48.9?% vs. 29/88, 33.0?%, P ?<?0.001). With WLE combined with LCI, intraobserver reproducibility signi?cantly improved, indicating that the combined approach can improve interobserver agreement compared with using WLE alone. Conclusions ?Endoscopic diagnosis of MCE using WLE combined with LCI images is effective. Intraobserver reproducibility and interobserver agreement in MCE can be improved when LCI is applied with conventional imaging (Clinical trial registration number: NCT03068572).

Dataset Information

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.

Publications

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.

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