Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2021; 27(46): 7982-7994
Published online Dec 14, 2021. doi: 10.3748/wjg.v27.i46.7982
Recombinant protein Schistosoma japonicum-derived molecule attenuates dextran sulfate sodium-induced colitis by inhibiting miRNA-217-5p to alleviate apoptosis
Li-Chao Zhang, Xiao-Ying Wu, Rui-Bing Yang, Fang Chen, Jia-Hua Liu, Yun-Yi Hu, Zhong-Dao Wu, Li-Fu Wang, Xi Sun
Li-Chao Zhang, Rui-Bing Yang, Jia-Hua Liu, Yun-Yi Hu, Zhong-Dao Wu, Xi Sun, Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
Xiao-Ying Wu, Department of Gastroenterology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Fang Chen, School of Medicine, South China University of Technology, South China University of Technology, Guangzhou 510000, Guangdong Province, China
Li-Fu Wang, Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Sun X contributed to the experiment design; Wu ZD, Yang RB, and Chen F contributed to the experiment implementation; Liu JH and Hu YY analyzed the data; Zhang LC and Wang LF conceived the experiments, performed the experiments, and wrote the manuscript; all authors participated in critical revision of the manuscript and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81902081 and No. 81871682; the Natural Science Foundation of Guangdong Province, No. 2020A1515011573 and No. 2019A1515012068; China Postdoctoral Science Foundation, No. 2018M640858 and No. 2019T120771; Fundamental Research Funds for the Central Universities, No. 19ykpy170, No. 17ykpy09 and No. 19ykpy29; National Science and Technology Major Project, No. 2018ZX10101002-001; the 111 Project, No. B12003; and the Natural Science Foundation of Guangdong Province, No. 2021A1515010976.
Institutional review board statement: The study was reviewed and approved by the Sun Yat-sen University Institutional Review Board.(Approval No. SYSU-IACUC-2019-B517).
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: I 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 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Fu Wang, DO, Research Scientist, Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, No. 74 Zhongshan Road, Guangzhou 510080, Guangdong Province, China. wanglf99999@163.com
Received: June 16, 2021
Peer-review started: June 16, 2021
First decision: June 30, 2021
Revised: July 9, 2021
Accepted: November 29, 2021
Article in press: November 29, 2021
Published online: December 14, 2021
Processing time: 176 Days and 23.1 Hours
Abstract
BACKGROUND

Inflammatory bowel disease (IBD) affects millions of people worldwide and has emerged as a growing problem in industrialized nations. The lack of therapeutic targets has limited the treatment of IBD. Studies found that parasitic nematode infections can ameliorate clinical and experimental colitis. Our previous study found that rSj16, a 16-kDa secreted protein of Schistosoma japonicum produced by Escherichia coli, has protective effects on dextran sulfate sodium (DSS)-induced colitis in mice. Apoptosis is an important factor in the pathogenesis of colitis. However, it is not clear whether the effect of rSj16 on colitis is related to apoptosis.

AIM

To investigate whether the protective effects of rSj16 on colitis is related to apoptosis and its mechanism.

METHODS

In-vivo, colitis was induced by DSS. The severity of colitis was assessed. WB was used to detect the changes of apoptosis-related genes in colon tissues. Q-PCR was used to detect the changes of miRNA-217-5p and HNF1B. In-vitro, WB was used to detect the changes of apoptosis-related genes in intestinal epithelial cells. TUNNEL staining and flow cytometry were used to detect cell apoptosis.

RESULTS

rSj16 attenuates clinical activity in DSS-induced colitis mice. TUNNEL staining and WB results showed that apoptosis was increased in colon tissue after treatment with DSS, and the apoptosis of colon tissue was significantly reduced after treatment with rSj16. Compared with normal mice, the expression of miR-217-5p was increased in colon tissue of DSS-induced colitis mice. In addition, the miR-217-5p target gene hnf1b was decreased after administration of DSS. After treatment with rSj16, the expression of miR-217-5p was decreased and the expression of HNF1B was increased compared with the DSS-treated group. When Etoposide was used in combination with miR-217-5p mimic on MODE-K cells, the expression of cleaved-Caspase-3 and Bax was increased, and Bcl-2 was decreased compared with only Etoposide treatment, the expression of HNF1B was significantly reduced, suggesting that miR-217-5p acts as a pro-apoptotic in colon epithelial cells and down-regulates the target gene hnf1b. After rSj16 administration in MODE-K cells, miR-217-5p expression was significantly decreased, HNF1B expression was increased, and apoptosis was reduced.

CONCLUSION

The protective effects of rSj16 on colitis is related to apoptosis and miRNA-217-5p may be a further target for therapeutic intervention against IBD.

Keywords: Schistosoma japonicum; rSj16; Inflammatory bowel disease; Apoptosis; miRNA-217-5p

Core Tip: The lack of therapeutic targets has limited the treatment of inflammatory bowel disease (IBD). Parasitic nematode infections can ameliorate clinical and experimental colitis. Our previous study found that rSj16, a 16-kDa secreted protein of Schistosoma japonicum produced by Escherichia coli, has protective effects on dextran sulfate sodium (DSS)-induced colitis in mice. We found that rSj16 can inhibit DSS-induced apoptosis in the colons of mice with colitis. In addition, we found that the inhibitory effect of rSj16 on apoptosis was associated with decreased miR-217-5p, and that hepatocyte nuclear factor 1 beta was increased after treatment with rSj16. These results highlight a novel therapeutic target that may be used to treat IBD.