Tu1856 MicroRNA Profiles and Their Relation to Proinflammatory Cytokines in Reflux Esophagitis

Abstract

Background and Aim: Growing interest has arisen regarding the mechanism of reflux esophagitis (RE) because RE is one of the risk factors of Barrett's esophagus leading to Barrett's adenocarcinoma. MicroRNA (miRNA) is involved and plays roles in immune and inflammatory disorders. However, there has been little information on the implication of miRNA in RE. In this study, we examined whether miRNAs are related to RE using rat models. Methods: A chronic acid reflux esophagitis model was made using rats by ligating forestomach and pylorus. Total RNAs were extracted two weeks after the procedures. We conducted 5 controls (sham rats) and 10 RE models. Using total RNAs from the controls and RE rats, miRNA expression patterns in RE mucosa were determined by comprehensive real-time PCR. In addition, We assessed the expression levels of interleukin (IL)-1 β, IL-6, MCP-1, INF-γ, CINC-1, TNF-α, MPO, CD68 and CD3emessenger RNA (mRNA) by qRT-PCR.We compared the miRNA and mRNA levels between the region of erosions (N=5) and non-erosions (N= 5), corresponding to Los Angeles M reflux esophagitis in humans. Results: The expression levels were significantly increased in 8 miRNAs, whereas 16 miRNAs were decreased. Especially, miR-223 (p,1×10-8) and miR-146b (p,1×10-5) were substantially increased in RE lesions. In contrast, miR-487b (p=0.002), miR-337-5p (p=0.002) and miR-543 (p=0.003) were substantially decreased in RE lesions. Out of cytokines examined, IL-6, TNFα, MCP1 and INF-γ were significantly up-regulated in RE mucosa (N=10) compared to those of sham control rats (N=5). Among the RE mucosa, 13 out of 24 miRNAs had significant correlations with at least one of the cytokines in expression. Especially, there were significant correlations between certain miRNAs (miR-223 and miR-146b) and IL-1 β, IL-6, TNF-α or INF-γ and CD68mRNA in RE mucosa. In RE rats, miR-146b expression level of erosive lesion was significantly up-regulated when compared to non-erosive lesion (p=0.038). Conclusion: There are the aberrant expressions of miRNAs in reflux esophagitis. Some of them were related to proinflammatory cytokines. Our study indicates that persistent RE may affect the mucosal expression profiles of miRNAs via chronic inflammation mediated by proinflammatory cytokines.