Novel therapeutic targets for gastroesophageal reflux disease by gene microarray profiling
Gastroesophageal reflux disease (GERD) is one of the most common GI-diagnosis. Proton pump inhibitors (PPIs) present the main treatment, but up to 40% of patients do not achieve adequate symptom control. Therefore the search continues for new therapeutic targets and additional treatment options. STW 5, a multi-component herbal preparation, was shown to relief concomitant reflux symptoms in patients with functional dyspepsia  and to prevent inflammation in an acute model of reflux esophagitis (RE) without affecting the pH of the refluxate . Recently, we showed that it also improved macroscopic and histological parameters of esophagitis in a subchronic model of RE in rats, where it down regulated proinflammatory cytokines in the tissue homogenates (proteome profiling) .
In the present study, we analyzed in our subchronic model of RE the transcript modulation in the esophageal tissue in an attempt to identify potential therapeutic targets. Rats were pre-treated for 7 d either with STW 5 (0.5 or 2 ml/kg) or omeprazole (O). Esophagitis was then induced surgically . Rats were treated for further 10 d with STW 5 or O and sacrificed. The esophagi were excised. RNA was isolated from defined tissue areas and transcripts were analyzed by Agilent whole genome microarray (rat). Selected genes were validated by RT-PCR.
Well known markers of inflammation and the immune response like IL-6, IL-1 and matrixmetallopeptidases (MMPs) were up-regulated in RE. Even though STW 5 and O down regulated different sets of genes, they showed a common pattern in a number of strongly and highly significantly regulated genes (p < 0.0001), including chemokine ligands 4 and 11, G-protein coupled receptor GPR84, the LOX-1 receptor and resistin.
Since gastric acid does not appear to be the only causative agent in GERD, identifying additional mechanisms involved in the pathogenesis or action of effective drugs may help detect novel therapeutic targets in GERD and pave the way for the development of effective treatment options.
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