Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2020; 26(48): 7619-7632
Published online Dec 28, 2020. doi: 10.3748/wjg.v26.i48.7619
Pretreatment with intestinal trefoil factor alleviates stress-induced gastric mucosal damage via Akt signaling
Yun Huang, Meng-Meng Wang, Zhi-Zhou Yang, Yi Ren, Wei Zhang, Zhao-Rui Sun, Shi-Nan Nie
Yun Huang, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong 226001, Jiangsu Province, China
Meng-Meng Wang, Zhi-Zhou Yang, Yi Ren, Wei Zhang, Zhao-Rui Sun, Shi-Nan Nie, Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
Shi-Nan Nie, Department of Emergency Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Author contributions: Huang Y and Wang MM contributed equally to this work; Sun ZR and Nie SN are co-corresponding authors for this work; Sun ZR and Nie SN designed the research; Huang Y and Wang MM carried out most of the experiments; Yang ZZ and Zhang W provided statistical support; Yang ZZ and Ren Yi performed some experiments; Huang Y, Wang MM, and Sun ZR contributed to manuscript preparation; All authors have read and approved the final manuscript.
Supported by Social Development Projects of Jiangsu Province, No. BE2017720; the National Natural Science Foundation of China, No. 81701894; Jiangsu Provincial Medical Youth Talent, No. QNRC2016909 and No. QNRC2016908; Natural Science Foundation of Jiangsu Province, No. BK20190247; Science Foundation of Jiangsu Health Commission, No. H2018039; China Postdoctoral Science Foundation, No. 2018M643890; Jiangsu Postdoctoral Science Foundation, No. 2018K048A and No. 2020Z193.
Institutional review board statement: The study was approved by the Review Board of Jinling Hospital, Medical School of Nanjing University.
Institutional animal care and use committee statement: The present study was approved by the Institution Animal Care and Use Committee of Jinling Hospital, Medical School of Nanjing University (No. 2019JLDWLLSC-016).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: There are no additional data available.
ARRIVE guidelines statement: The manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Shi-Nan Nie, MD, PhD, Director, Professor, Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China. shn_nie@sina.com
Received: September 28, 2020
Peer-review started: September 28, 2020
First decision: November 8, 2020
Revised: November 19, 2020
Accepted: December 6, 2020
Article in press: December 6, 2020
Published online: December 28, 2020
Processing time: 88 Days and 6.7 Hours
ARTICLE HIGHLIGHTS
Research background

Stress-related gastric mucosal damage is a prevalent complication in critically ill patients in the intensive care unit, and it may evolve to ulceration and bleeding. Stress ulcer prophylaxis has been common in routine intensive care, but with controversy. Co-secreted with mucins, intestinal trefoil factor (ITF) is reported to promote the restitution and regeneration of intestinal mucosal epithelium, but the mechanism is unknown.

Research motivation

As an endogenous peptide, ITF harbors innate advantages over conventional anti-ulcer agents, and might be a new candidate for stress ulcer prophylaxis.

Research objectives

To investigate the protective effects of ITF on gastric mucosa and explore the underlying mechanisms.

Research methods

We utilized water immersion restraint stress-induced gastric mucosal damage rat model and lipopolysaccharide-induced gastric epithelium cell damage model to investigate the potential functions of ITF on damaged gastric mucosa both in vivo and in vitro.

Research results

We found that ITF promoted proliferation and migration and inhibited necrosis of gastric epithelium cells and preserved the integrity of gastric mucosa by increasing expression of occludin and zonula occludens-1. Additionally, pretreatment with ITF ameliorated the gastric mucosal epithelial damage and promoted mucosal repair in vivo. We found that the protective effects of ITF were exerted by activation of Akt signaling, and the specific inhibitor of this pathway, LY249002, abolished the protective effects.

Research conclusions

Pretreatment with ITF alleviated stress-induced gastric mucosal damage by activation of Akt signaling.

Research perspectives

This study provides insight into the translational potential of ITF as a promising candidate for prevention and treatment of stress-induced gastric mucosal damage.