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. The mediodorsal thalamic nucleus (MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.
To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate 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 and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. 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 revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanism through which RWIS gives rise to SGU.
Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.
Core tip: Quantitative proteomic analysis was used to screen for differentially expressed proteins in the mediodorsal thalamic nucleus of rats subjected to restraint water-immersion stress. A total of 65 dysregulated proteins were identified, which are mainly involved in the neurological disease signalling pathways. Meanwhile, the 31 upregulated proteins are primarily related to cell division, whereas the 34 downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Furthermore, glycogen synthase kinase-3 beta might be related to the central mechanism through which restraint water-immersion stress gives rise to stress-induced gastric ulcer (SGU). Proteomic analysis elucidated the nervous system molecular targets of SGU.