Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2019; 25(41): 6222-6237
Published online Nov 7, 2019. doi: 10.3748/wjg.v25.i41.6222
MiR-32-5p aggravates intestinal epithelial cell injury in pediatric enteritis induced by Helicobacter pylori
Jing Feng, Jian Guo, Jun-Ping Wang, Bao-Feng Chai
Jing Feng, Bao-Feng Chai, Institute of Loess Plateau, Shanxi University, Taiyuan 030006, Shanxi Province, China
Jing Feng, Jun-Ping Wang, Department of Gastroenterology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Jian Guo, Department of General Surgery, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Author contributions: Chai BF and Wang JP designed the research; Feng J and Guo J performed the research; Feng J and Chai BF analyzed the data; Feng J and Wang JP wrote the paper.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Shanxi University and Ethics Committee of Shanxi Provincial People's Hospital, Shanxi Province, China.
Conflict-of-interest statement: There was no competing interest.
Data sharing statement: All the data in the current research are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Bao-Feng Chai, MD, PhD, Professor, Institute of Loess Plateau, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, Shanxi Province, China. 13644359409@163.com
Telephone: +86-13603583312
Received: January 26, 2019
Peer-review started: August 27, 2019
First decision: September 19, 2019
Revised: October 11, 2019
Accepted: October 22, 2019
Article in press: October 22, 2019
Published online: November 7, 2019
Processing time: 71 Days and 15.8 Hours
Abstract
BACKGROUND

Pediatric enteritis is one of the infectious diseases in the digestive system that causes a variety of digestive problems, including diarrhea, vomiting, and bellyache in children. Clinically, Helicobacter pylori (H. pylori) infection is one of the common factors to cause pediatric enteritis. It has been demonstrated that aberrant expression of microRNAs (miRNAs) is found in gastrointestinal diseases caused by H. pylori, and we discovered a significant increase of miR-32-5p in H. pylori-related pediatric enteritis. However, the exact role of miR-32-5p in it is still unknown.

AIM

To investigate the role of aberrant miR-32-5p in pediatric enteritis induced by H. pylori.

METHODS

MiR-32-5p expression was detected by quantitative real time-polymerase chain reaction. The biological role of miR-32-5p in H. pylori-treated intestinal epithelial cells was evaluated by Cell Counting Kit-8 assay and flow cytometry. The potential target of miR-32-5p was predicted with TargetScanHuman and verified by luciferase assay. The downstream mechanism of miR-32-5p was explored by using molecular biology methods.

RESULTS

We found that miR-32-5p was overexpressed in serum of H. pylori-induced pediatric enteritis. Further investigation revealed that H. pylori infection promoted the death of intestinal epithelial cells, and increased miR-32-5p expression. Moreover, miR-32-5p mimic further facilitated apoptosis and inflammatory cytokine secretion of intestinal epithelial cells. Further exploration revealed that SMAD family member 6 (SMAD6) was the direct target of miR-32-5p, and SMAD6 overexpression partially rescued cell damage induced by H. pylori. The following experiments showed that miR-32-5p/SMAD6 participated in the apoptosis of intestinal epithelial cells induced by transforming growth factor-β-activated kinase 1 (TAK1)-p38 activation under H. pylori infection.

CONCLUSION

Our work uncovered the crucial role of aberrant expression of miR-32-5p in H. pylori–related pediatric enteritis, and suggested that the TAK1-p38 pathway is involved in it.

Keywords: MiR-32-5p; SMAD family member 6; Transforming growth factor-β-activated kinase 1; Apoptosis; Enteritis; Helicobacter pylori

Core tip: Our study demonstrated the harmful role of aberrant miR-32-5p in Helicobacter pylori (H. pylori)-infected intestinal epithelial cells. Further investigation showed that SMAD family member 6 (SMAD6) was the downstream of miR-32-5p and exerted an opposite role in this process. What’s more, miR-32-5p/SMAD6 contributed to transforming growth factor-β-activated kinase 1-p38 cascade activation in intestinal epithelial cells under H. pylori infection. These findings provide a novel insight into the pathogenesis of pediatric enteritis caused by H. pylori.