Identification and immunoinfiltration analysis of key genes in ulcerative colitis using WGCNA

Siyi Ni; Yingchao Liu; Jihong Zhong; Yan Shen

doi:10.7717/peerj.16921

Identification and immunoinfiltration analysis of key genes in ulcerative colitis using WGCNA

PeerJ. 2024 Feb 26:12:e16921. doi: 10.7717/peerj.16921. eCollection 2024.

Authors

Siyi Ni¹, Yingchao Liu¹, Jihong Zhong¹, Yan Shen¹

Affiliation

¹ Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Abstract

Objective: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by an unclear pathogenesis. This study aims to screen out key genes related to UC pathogenesis.

Methods: Bioinformatics analysis was conducted for screening key genes linked to UC pathogenesis, and the expression of the screened key genes was verified by establishing a UC mouse model.

Results: Through bioinformatics analysis, five key genes were obtained. Subsequent infiltration analysis revealed seven significantly different immune cell types between the UC and general samples. Additionally, animal experiment results illustrated markedly decreased body weight, visible colonic shortening and damage, along with a significant increase in the DAI score of the DSS-induced mice in the UC group in comparison with the NC group. In addition, H&E staining results demonstrated histological changes including marked inflammatory cell infiltration, loss of crypts, and epithelial destruction in the colon mucosa epithelium. qRT-PCR analysis indicated a down-regulation of ABCG2 and an up-regulation of IL1RN, REG4, SERPINB5 and TRIM29 in the UC mouse model. Notably, this observed trend showed a significant dependence on the concentration of DSS, with the mouse model of UC induced by 7% DSS demonstrating a more severe disease state compared to that induced by 5% DSS.

Conclusion: ABCG2, IL1RN, REG4, SERPINB5 and TRIM29 were screened out as key genes related to UC by bioinformatics analysis. The expression of ABCG2 was down-regulated, and that of IL1RN, REG4, SERPINB5 and TRIM29 were up-regulated in UC mice as revealed by animal experiments.

Keywords: Bioinformatics analysis; Immunoinfiltration analysis; Ulcerative colitis; WGCNA.

MeSH terms

Animals
Colitis, Ulcerative* / chemically induced
Down-Regulation / genetics
Inflammatory Bowel Diseases*
Mice
Pancreatitis-Associated Proteins / genetics

Substances

REG4 protein, mouse
Pancreatitis-Associated Proteins

Grants and funding

This study was supported by the Zhejiang Medical Association Project (2019ZYC-B01) and the Zhejiang Traditional Chinese Medicine Science and Technology Program (2023ZL061). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.