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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis
Ye Tian, Xin Li, Xu Wang, Si-Ting Pei, Hong-Xin Pan, Yu-Qi Cheng, Yi-Chen Li, Wen-Ting Cao, Jin-Dong Ding Petersen, Ping Zhang
Ye Tian, Si-Ting Pei, Hong-Xin Pan, Wen-Ting Cao, Jin-Dong Ding Petersen, Ping Zhang, International School of Public Health and One Health, Hainan Medical University, Haikou 571199, Hainan Province, China
Xin Li, Yu-Qi Cheng, Yi-Chen Li, Medical Laboratory Science and Technology College, Harbin Medical University - Daqing Campus, Daqing 163000, Heilongjiang Province, China
Xu Wang, Department of Laboratory Diagnosis, Qiqihar Tuberculosis Control Center, Qiqihar 161000, Heilongjiang Province, China
Jin-Dong Ding Petersen, Department of Public Health, University of Copenhagen, Copenhagen 1353, Denmark
Jin-Dong Ding Petersen, Department of Public Health, University of Southern Denmark, Odense 5000, Denmark
Co-first authors: Ye Tian and Xin Li.
Author contributions: Petersen JDD and Zhang P initiated the study; Tian Y, Li X, and Wang X contributed equally to this study; Li X and Wang X conducted the experiments; Tian Y wrote the manuscript; Pei ST, Pan HX, Cheng YQ, and Li YC conducted the preliminary data analysis; Zhang P contributed to the preliminary data analysis supervision; Cao WT reviewed and reanalyzed the data and confirmed the authenticity of the data. All of the authors discussed the results, commented on the manuscript, and approved the publication submission.
Supported by the Natural Science Foundation of Hainan Province, No. 823MS046; and the Talent Program of Hainan Medical University, No. XRC2022007.
Institutional animal care and use committee statement: This study was conducted in strict accordance with ethical guidelines for animal research. All experimental animals were housed in a controlled environment. Isoflurane was used for anesthesia prior to operations to minimize pain and discomfort. The experimental protocols involving animals were carefully designed to reduce suffering and were reviewed and approved by the Ethics Committee of Hainan Medical University (Approval No. HYLL-2022-128).
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available. The data for this study are available upon request to the corresponding author pending approval from Hainan Medical University.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and 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 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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ping Zhang, MD, PhD, Professor, International School of Public Health and One Health, Hainan Medical University, No. 3 Xueyuan Road, Haikou 571199, Hainan Province, China. pingzhang@hainmc.edu.cn
Received: October 12, 2023
Peer-review started: October 12, 2023
First decision: December 8, 2023
Revised: December 26, 2023
Accepted: January 29, 2024
Article in press: January 29, 2024
Published online: March 14, 2024
Processing time: 154 Days and 10.4 Hours
ARTICLE HIGHLIGHTS
Research background
Ulcerative colitis (UC) is a chronic inflammatory condition of the colon with unknown causes. Alkaline sphingomyelinase (alk-SMase), expressed in intestinal epithelial cells, shows anti-inflammatory effects, but its mechanism remains to be clarified.
Research motivation
This study was motivated by the need to understand the mechanism behind the anti-inflammatory effects of alk-SMase, particularly in relation to intestinal barrier function and oxidative stress in dextran sulfate sodium (DSS)-induced colitis.
Research objectives
The primary objective was to explore how alk-SMase impacts intestinal barrier function and manages oxidative stress, contributing to its anti-inflammatory role in DSS-induced colitis.
Research methods
Mice were given 3% DSS drinking water to induce colitis. The study assessed disease activity, intestinal permeability, bacterial translocation, and the ultrastructure of intestinal epithelial cells. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were employed to evaluate intestinal barrier proteins and mRNA, and serum oxidant and antioxidant levels were analyzed.
Research results
In gene knockout (KO) mice, inflammation and intestinal permeability were more severe compared to wild-type mice after DSS induction. There was a significant reduction in intestinal barrier proteins and an increase in serum malondialdehyde levels, indicating lower antioxidant capacity. Notably, the administration of the nuclear factor erythroid 2-related factor 2 (Nrf2) activator tertiary butylhydroquinone (t-BHQ) relieved colitis in KO mice.
Research conclusions
This study introduces the model that alk-SMase regulates intestinal barrier stability and antioxidant activity via the Nrf2 pathway, offering a new perspective on managing colitis. We employed a novel approach by using alk-SMase KO mice and treating them with t-BHQ to isolate and understand the specific effects of alk-SMase and Nrf2 in colitis.
Research perspectives
The findings underscore the potential of alk-SMase in maintaining intestinal barrier stability and increasing antioxidant capacity, offering insights into novel therapeutic approaches for colitis. Future research will delve into the mechanisms by which alk-SMase influences the Nrf2 pathway, further illuminating its therapeutic potential in colitis.
