Published online Nov 7, 2019. doi: 10.3748/wjg.v25.i41.6222
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
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.
To investigate the role of aberrant miR-32-5p in pediatric enteritis induced by H. pylori.
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.
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.
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.
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.