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
Abstract
BACKGROUND

Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients. Stress ulcer prophylaxis has been part of routine intensive care, but uncertainty and controversy still exist. Co-secreted with mucins, intestinal trefoil factor (ITF) is reported to promote restitution and regeneration of intestinal mucosal epithelium, although the mechanism remains unknown.

AIM

To elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms.

METHODS

We used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro.

RESULTS

ITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro. It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1. In the rat model, pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair. The protective effects of ITF were confirmed to be exerted via activation of Akt signaling, and the specific inhibitor of Akt signaling LY249002 reversed the protective effects.

CONCLUSION

ITF might be a promising candidate for prevention and treatment of stress-induced gastric mucosal damage, and further studies should be undertaken to verify its clinical feasibility.

Keywords: Intestinal trefoil factor; Water immersion restraint stress; Gastric mucosa; Epithelium integrity; Akt signaling pathway

Core Tip: Stress-related gastric mucosal damage remains an issue for critical care patients. As an endogenous peptide, intestinal trefoil factor was found to alleviate both macroscopic and microscopic gastric mucosal damage in vivo induced by acute stress stimulation and promote mucosal epithelial cell survival, accelerate wound closure, and preserve mucosal integrity in vitro. Akt signaling pathway could play an essential role. Therefore, intestinal trefoil factor is a promising candidate for prevention and treatment of stress-induced gastric mucosal damage.