Title |
GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis
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Published in |
Molecular Medicine, November 2015
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DOI | 10.2119/molmed.2015.00098 |
Pubmed ID | |
Authors |
Heba Abdel-Aziz, Mathias Schneider, Winfried Neuhuber, Abdel Meguid Kassem, Saleem Khailah, Jürgen Müller, Hadeel Gamal Eldeen, Ahmed Khairy, Mohamed T. Khayyal, Anastasiia Shcherbakova, Thomas Efferth, Gudrun Ulrich-Merzenich |
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 non-uniform 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 sub-chronic 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 cellline 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 pro-inflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was up-regulated 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 up-regulated 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. |
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Unknown | 1 | 100% |
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Members of the public | 1 | 100% |
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 9 | 22% |
Researcher | 7 | 17% |
Student > Master | 5 | 12% |
Student > Bachelor | 3 | 7% |
Other | 3 | 7% |
Other | 6 | 15% |
Unknown | 8 | 20% |
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Medicine and Dentistry | 10 | 24% |
Agricultural and Biological Sciences | 6 | 15% |
Immunology and Microbiology | 3 | 7% |
Biochemistry, Genetics and Molecular Biology | 2 | 5% |
Other | 3 | 7% |
Unknown | 6 | 15% |