Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2911
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
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.
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.
To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate the molecular mechanisms of SGU.
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.
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.
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.
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.