Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2019; 25(23): 2911-2923
Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2911
Proteomics of the mediodorsal thalamic nucleus of rats with stress-induced gastric ulcer
Sheng-Nan Gong, Jian-Ping Zhu, Ying-Jie Ma, Dong-Qin Zhao
Sheng-Nan Gong, Jian-Ping Zhu, Ying-Jie Ma, Dong-Qin Zhao, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong Province, China
Author contributions: Zhao DQ and Zhu JP designed the experiments; Ma YJ and Gong SN performed the experiments; Zhao DQ performed mass spectrometry analysis and wrote the manuscript; Gong SN analyzed the protemoics data; Zhu JP analyzed the GM and EI data; Ma YJ analyzed the WB data; all the authors approved the final version of the manuscript for publication.
Supported by National Natural Science Foundation of China, No. 31501861; and Natural Science Foundation of Shandong Province, China, No. ZR2015CM013.
Institutional animal care and use committee statement: All procedures were approved by the Institutional Animal Care and Use Committee of Shandong Normal University (Jinan, People’s Republic of China; No. AEECSDNU2018003).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
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 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:
Corresponding author: Dong-Qin Zhao, PhD, Associate Professor, College of Life Sciences, Shandong Normal University, No. 88, East Wenhua Road, Lixia District, Jinan 250014, Shandong Province, China.
Telephone: +86-531-86180745
Received: January 27, 2019
Peer-review started: January 27, 2019
First decision: March 20, 2019
Revised: May 8, 2019
Accepted: May 18, 2019
Article in press: May 18, 2019
Published online: June 21, 2019
Research background

Stress-induced gastric ulcer (SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress (RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. We have focused on providing a resource for determining the molecular regulatory mechanisms of stress-induced gastric mucosal lesion since 1990s. The mediodorsal thalamic nucleus (MD) is the centre integrating visceral and physical activity. There is remarkable Fos expression in the MD of rats subjected to RWIS.

Research motivation

iTRAQ becomes a powerful tool to explore the response in proteins to stress. A comparative proteomic analysis of RWIS-exposed and control rats might not only shed light on the role of the MD in gastrointestinal dysfunction induced by RWIS but also contribute to the detection of proteomic differences and the identification of targets for more specific therapies.

Recearch objectives

To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate the molecular mechanisms of SGU.

Research methods

Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index (EI) and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chro-matography and tandem mass spectrometry (LC–MS/MS). Additionally, iTRAQ results were verified by Western blot analysis.

Research results

A total of 2853 proteins were identified, and these included 65 dysregulated (31 upregulated and 34 downregulated) proteins (fold change ratio ≥ 1.2). Gene Ontology (GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis (IPA) analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta (GSK3B) might be related to the central mechanism through which RWIS gives rise to SGU.

Research conclusions

Quantitative proteomic analysis elucidates the molecular targets associated with the production of SGU and provides insights into the effects of the MD. The underlying molecular mechanisms need to be further dissected.

Research perspectives

This study provides resources for identifying the biological functions of dysregulated proteins and dissecting pathways that could aid the identification of the molecular regulatory mechanism of SGU. The functions of key proteins linked to gastric ulcer, e.g., GSK3B, during RWIS should later be verified by qrt-pCR or immunoblotting, and further functional studies using RNAi.