Abstract

Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease. However, the role of exosomal microRNAs (miRNAs) and esophageal miRNAs in GERD has not been studied. A rat model of acid reflux esophagitis was used to establish a novel diagnosis marker for GERD and examine dynamics of miRNA expression in GERD. Rats were sacrificed 3 (acute phase), 7 (sub-acute phase) and 21 days (chronic phase) after induction of esophagitis. Exosomes were extracted from serum, and the expression patterns of serum miRNAs were analyzed. Four upregulated miRNAs (miR-29a-3p, 128-3p, 223-3p and 3473) were identified by microarray analysis. The expression levels of exosomal miR-29a-3p were significantly higher in the chronic phase of reflux esophagitis compared with controls, and increased expression of miR-29a-3p was specific to chronic reflux esophagitis. Esophageal miR-223-3p expression was higher compared with controls, and gradually decreased from acute to chronic phase in esophagitis. In conclusion, exosomal miR-29a-3p and esophageal miR-223-3p might play roles in GERD.

Highlights

  • Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease that is divided into two subtypes: erosive reflux disease (ERD) and non-erosive reflux disease (NERD), the latter being defined as the presence of troublesome reflux symptoms without esophageal mucosal breakage [1]

  • The membrane-bound aim of this study was that to observe of exosomal andby esophageal to establish vesicles are 40–100changes nm in diameter and secreted various cells,miRNAs indicated that miRNAs markers may be potentially useful clinical diagnostic or prognostic tools expression novel diagnosis for GERD

  • 21 compared compared with with the the control control. These results revealed that only miR-29a-3p expression significantly increased (Figure 2D). These results revealed that only miR-29a-3p expression significantly increased in in the the chronic chronic phase phase of of reflux reflux esophagitis, esophagitis, suggesting suggesting exosomal exosomal miR-29a-3p miR-29a-3p might might be be aa novel novel candidate candidate surrogate surrogatemarker markerfor forchronic chronicreflux refluxesophagitis

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Summary

Introduction

Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease that is divided into two subtypes: erosive reflux disease (ERD) and non-erosive reflux disease (NERD), the latter being defined as the presence of troublesome reflux symptoms without esophageal mucosal breakage [1]. Membrane-bound vesicles that are 40–100 nm in diameter and secreted by various cells, indicated (miRNAs) are small, as non-coding that control gene expression annealing to that miRNAsMicroRNAs may be potentially useful clinical RNAs diagnostic or prognostic toolsby[9,10,11,12]. The membrane-bound aim of this study was that to observe of exosomal andby esophageal to establish vesicles are 40–100changes nm in diameter and secreted various cells,miRNAs indicated that miRNAs markers may be potentially useful clinical diagnostic or prognostic tools expression [9,10,11,12]. The aim of Results this study was to observe changes of exosomal and esophageal miRNAs to establish novel diagnosis markers for GERD and to examine dynamics of miRNA expression using a rat model

Results
Unique Expression Pattern of Exosomal miRNA in Reflux Esophagitis
Relative
Expression
The Relationship between miR-223-3p and mRNA in Esophageal Tissue
Discussion
Materials and Methods
Isolation of Serum Exosomes and RNA Extraction
Microarray Analysis
Real-Time qPCR for miRNA
Real-Time qPCR for mRNA
Statistical Analyses
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