Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2018; 24(6): 706-715
Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.706
Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS-induced colitis in rats
Chun-Lan Xu, Yu Guo, Lei Qiao, Li Ma, Yi-Yi Cheng
Chun-Lan Xu, Yu Guo, Lei Qiao, Li Ma, Yi-Yi Cheng, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, Shaanxi Province, China
Author contributions: Xu CL conceived and designed the experiments; Guo Y, Qiao L and Ma L performed the experiments; Cheng YY analyzed the data; Roman A contributed reagents/materials/analysis tools; Xu CL wrote the manuscript.
Supported by the National Natural Science Foundation of China, No. 31672435; the Graduate Starting Seed Fund of Northwestern Polytechnical University, No. Z2017236; and the National College Students Innovation, Experiment Program, No. 201610699266.
Institutional review board statement: The study was reviewed and approved by the Northwestern Polytechnical University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Northwestern Polytechnical University (IACUC protocol number: No.2016014).
Conflict-of-interest statement: No potential conflicts of interest.
Data sharing statement: No additional data are available.
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/
Correspondence to: Chun-Lan Xu, PhD, Associate Professor, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyixi Road, Xi’an 710072, Shaanxi Province, China. clxu@nwpu.edu.cn
Telephone: +86-29-88460543 Fax: +86-29-88460332
Received: December 1, 2017
Peer-review started: December 1, 2017
First decision: December 13, 2017
Revised: December 19, 2017
Accepted: December 27, 2017
Article in press: December 27, 2017
Published online: February 14, 2018
Processing time: 67 Days and 1.8 Hours
ARTICLE HIGHLIGHTS
Research background

Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD) Prolonged inflammation of the intestinal tract affects the patients’ quality of life and increases the risk of colorectal cancer development. Endogenous antimicrobial and immunoregulatory peptides represent an emerging category of therapeutic agents, are gaining considerable interest in the scientific community. VIP is a neuropeptide with potent anti-inflammatory activities. Recombinant expressed VIP analogue with higher antimicrobial activity and stability than natural peptide was produced by an effective and low-cost production method. The results indicated that rVIPa alleviated TNBS-induced colitis via TLR4/NF-κB-mediated signaling pathway. rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders. The study contributes to advancement in novel treatment design.

Research motivation

At present, a proportion of patients with Crohn’s disease could not obtain high efficacy of the available medical therapies. Therefore, it is urgent to develop new anti-inflammatory agents with high efficacy, safety and low cost. The natural biological peptides and their analogues will provide important and significant resources for the development of molecules that can block inflammatory pathways.

Research objectives

rVIPa with high antimicrobial activity and stability was produced by an effective and low-cost biotechnology. The current study was conducted to investigate the modulatory effect of rVIPa on colon in rats with TNBS-induced colitis. The study contributes to the development of a kind of new and novel therapeutic agent from endogenous bioactive peptides for IBD.

Research methods

The current study investigated the anti-inflammatory activity, and the possible mechanism of rVIPa through establishing acute colitis model in rats administrated of TNBS intrarectally. In addition to the body weight change, histological assessment, MPO and endotoxin analyzed by ELISA, and tight junction proteins levels analyzed by Western Blot, TLR4/NF-κB-mediated signaling pathway were also investigated.

Research results

The current study first find that VIP analogue produced by recombinant expression significantly ameliorates the colon injury and inflammation caused by TNBS in rats, and exhibits a protective effect on colitis. Moreover, administration with rVIPa inhibited proinflammatory cytokines, up-regulated tight junction proteins expression, and promotion of anti-inflammatory cytokines via TLRs/NF-κB signaling pathway.

Research conclusions

rVIPa alleviated TNBS-induced inflammation and effectively protected the intestinal mucosal barrier function in rats, which may be related to TLR4/NF-κB-mediated signaling pathway. These results suggested that rVIPa could be explored to a new alternative therapy for intestinal inflammatory disorders.

Research perspectives

By rational design and molecular modification, the antimicrobial and anti-inflammatory activity, and stability for endogenous bioactive peptides could be further improved. This study provides a simple, low-cost strategy for identifying and producing a novel anti-inflammatory agent from human innate host defense mechanisms in the process of biological evolution.