Transcriptome and methylome profiling in a rat model of irritable bowel syndrome induced by stress

Zhu,Shengtao; Min,Li; Guo,Qingdong; Li,Hengcun; Yu,Yang; Zong,Ye; Wang,Liyong; Li,Peng; Gu,Junchao; Zhang,Shutian

doi:10.3892/ijmm.2018.3823

Transcriptome and methylome profiling in a rat model of irritable bowel syndrome induced by stress

Authors:
- Shengtao Zhu
- Li Min
- Qingdong Guo
- Hengcun Li
- Yang Yu
- Ye Zong
- Liyong Wang
- Peng Li
- Junchao Gu
- Shutian Zhang
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Affiliations: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100050, P.R. China, Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China
Published online on: August 14, 2018 https://doi.org/10.3892/ijmm.2018.3823
Pages: 2641-2649
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is associated with psychological stress. However, the full landscape of IBS‑related epigenetic factors remains unveiled and needs to be elucidated. The water‑avoidance stress (WAS) method was used to induce a rat IBS model. Each rat was monitored, and its defecation and behavior were recorded. Total colon RNA was isolated and subjected to Affymetrix GeneChip analysis. Reduced Representation Bisulfate Sequencing (RRBS) was applied to determine the genome‑wide methylation pattern in both IBS and control rats. Rats with IBS egested a significantly increased amount of dry and loose stools compared with the control animals, without significant changes in body weight. Compared with the control group, 309 genes were upregulated and 224 genes were downregulated in the colon of the IBS rats. Notch signaling and focal adhesion were increased in the differentially expressed genes (DEGs). A total of 541 genes had significant lower methylation level and 626 genes had significantly higher methylation level in their promoter regions. Adherens junction and leukocyte transendothelial migration were enriched in the differentially methylated genes (DMGs). Few genes were identified in common in both DEGs and DMGs, suggesting that gene expression was not altered by promoter methylation. Reverse transcription‑quantitative polymerase chain reaction validation revealed that the mRNA levels of SSX2IP, PARD3 and VCL were significantly downregulated in the IBS group, in accordance with hypermethylation of their promoters. In summary, the present study used a WAS‑induced IBS rat model to provide transcriptome and methylome profiling. Most DEGs were associated with Notch signaling and focal adhesion, and only a few were altered by promoter methylation. The present results demonstrated that psychological stress could influence the integrity of the intestinal mucosa barrier and regulate inflammatory response.

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