Copyright
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Herbs-partitioned moxibustion alleviates aberrant intestinal epithelial cell apoptosis by upregulating A20 expression in a mouse model of Crohn’s disease
Jing Zhou, Lu-Yi Wu, Liu Chen, Ya-Jing Guo, Yi Sun, Tao Li, Ji-Meng Zhao, Chun-Hui Bao, Huan-Gan Wu, Yin Shi
Jing Zhou, Liu Chen, Ya-Jing Guo, Yi Sun, Tao Li, Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Lu-Yi Wu, Qigong Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
Ji-Meng Zhao, Chun-Hui Bao, Huan-Gan Wu, Yin Shi, Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Ji-Meng Zhao, Chun-Hui Bao, Huan-Gan Wu, Key Laboratory of Acupuncture and Immunological Effects, Shanghai Institute of Acupuncture-Moxibustion and Meridian, Shanghai 200030, China
Yin Shi, Outpatient Department, Shanghai Institute of Acupuncture-Moxibustion and Meridian, Shanghai 200030, China
Author contributions: Zhou J, Shi Y, and Wu HG designed the research; Zhou J, Chen L, Zhao JM, Guo YJ, Sun Y, and Li T performed the experiments; Wu LY, Zhou J, and Bao CH collected and analyzed the data; Zhou J wrote the manuscript; all authors reviewed the manuscript prior to its submission, and read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81273844 and No. 81473757; National Key Basic Research Program of China (973 Program), No. 2015CB554500; and Shanghai Rising-Star Program, No. 16QA1403400.
Institutional animal care and use committee statement: All animal experiments in this study were performed under guidelines approved by the Animal Ethics Committee of the Shanghai University of Traditional Chinese Medicine (No. 2013025).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The manuscript was prepared according to the ARRIVE guidelines.
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: Yin Shi, PhD, Doctor, Professor, Outpatient Department, Shanghai Institute of Acupuncture-Moxibustion and Meridian, 650 South Wanping Road, Shanghai 200030, China. flysy0636@163.com
Telephone: +86-21-64383910 Fax: +86-21-64390339
Received: January 13, 2019
Peer-review started: January 14, 2019
First decision: February 13, 2019
Revised: March 13, 2019
Accepted: March 15, 2019
Article in press: March 16, 2019
Published online: May 7, 2019
ARTICLE HIGHLIGHTS
Research background
A20, as an intestinal epithelium protector, plays a critical role in anti-apoptosis in Crohn’s disease. Previous studies have indicated a beneficial role of herbs-partitioned moxibustion (HPM) in Crohn’s disease by decreasing intestinal epithelial apoptosis. However, whether the effect of HPM is through A20 is unclear.
Research motivation
Our findings will suggest a role of HPM in regulating A20 level in anti-apoptotic pathway in the intestinal epithelium of mice with Crohn’s disease.
Research objectives
To explore whether HPM alleviates cell apoptosis in the intestinal epithelium by upregulating A20 level in Crohn’s disease.
Research methods
Two types of mice were included in this study, namely, mice with A20 deletion in intestinal epithelial cells (A20IEC-KO) and wild-type mice. Both of them were randomly divided into normal control (NC), model control (MC), mesalazine (MESA), and HPM groups. 2,4,6-trinitrobenzene sulfonic acid (TNBS) was administered to establish a Crohn’s disease model in the two types. The morphology of the colonic mucosa, serum endotoxin, apoptosis of epithelial cells, protein levels of A20 and tumor necrosis factor receptor (TNFR) 1-related signaling molecules, co-expression of A20 and TNFR1-associated death domain (TRADD), and co-expression of A20 and receptor-interacting protein (RIP) 1 were observed. All data are presented as the mean ± standard deviation.
Research results
Compared with A20IEC-KO mice, wild-type mice in the HPM group showed that damage of intestinal epithelial barrier was improved, serum endotoxin levels were significantly downregulated (P < 0.01), apoptosis percentages were significantly decreased (P < 0.01), A20 level was significantly upregulated (P < 0.01), and TNFR1, TRADDD, and RIP1 levels were downregulated (PTNF-a < 0.01, PTNFR1 < 0.05, PTRADD < 0.05, PRIP1 < 0.05). In addition, the co-expression of A20/TRADD and A20/RIP1 showed a predominant yellow fluorescence in WT HPM mice, while a predominantly red fluorescence was noted in A20IEC-KO HPM mice.
Research conclusions
HPM can upregulate A20 level, resulting in decreased expression of TNFR1, TRADD, and RIP1 to alleviate aberrant cell apoptosis in the intestinal epithelial barrier in Crohn’s disease.
Research perspectives
Effect of HPM in decreasing cell apoptosis of intestinal epithelial cells is through upregulating A20 level in Crohn’s disease.
