Document Type : Research Paper

Authors

1 Department of Cellular and Molecular Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran,

2 Department of Cellular and Molecular Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran,- Laboratory of tissue and embryology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran,

3 Laboratory of Tissue and Embryology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

10.30498/ijb.2024.361840.3502

Abstract

Background: Our knowledge of Type 1 Diabetes Mellitus (T1DM) etiology is incomplete; however, the pathogenesis of
the disease includes T-cell-mediated destruction of β-cells.

Objective:  The present study aimed to investigate the key gene pathways and co-expression networks in T1DM disease.

Material and Methods:  TIDM-associated genes were identified from 13 databases, enrichment of pathways annotated with functional annotations, and analysis of protein-protein network interactions. Next, functional modules and transcription factor networks were constructed. The analysis of gene co-expression networks was conducted to discover associated pivotal modules
Results: A total of 172 expressed genes and four variants (SNP) were filtered in the of T1DM disease; pathway enrichment analysis identified key pathways, such as inflammatory bowel disease, type I diabetes mellitus, cytokine-cytokine receptor interaction, Th17 cell differentiation, JAK-STAT signaling pathway, and graft-versus-host disease. A weighted correlation network analysis revealed one module that was strongly correlated with T1DM. Functional annotation revealed that the module was mainly enriched in pathways such as T cell activation, regulation of immune system process, and response to the organic substance. IRF2, IRF4, IRF8, and CDX2 were regulated in the module at a significant level.
Conclusion:  The study identified IL-2 as a significant T1DM hotspot and highlighted the role of hub genes and transcription factors in the autoimmune disease, offering potentials for treatment and prevention.

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