Investigating metabolite-protein interactions reveals novelmolecular insights in pemphigus vulgaris
نویسندگان
1 Student Research Committee, Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
doi
10.22034/ijd.2025.544860.2094چکیده
Background: Pemphigus Vulgaris (PV) is a chronic autoimmune blistering disease characterized by lesions in the oral mucosa. Metabolites play a significant role in the development and progression of PV through their involvement in various metabolic processes. This study aimed to identify the key metabolites and genes associated with PV, as well as their functions, to facilitate the development of promising therapeutic approaches.Methods: High-scoring genes associated with PV were identified from the DISEASES database to construct a protein-protein interaction (PPI) network. A PPI network comprising these high-score genes and chemical compounds was generated using the STITCH plugin in Cytoscape software. Metabolites were distinguished from compounds based on data from the Metabolic Atlas and PubChem databases. Sub-networks, each containing a specific metabolite and its firstdegree neighboring genes, were analyzed, and the key elements were selected for further investigation. The central nodes within these critical sub-networks were evaluated through gene ontology analysis.Results: Findings indicate that MgADP, Ins (1,3,4,5) P4, PtdIns (3,4,5) P3, and hexanoic acid are the primary metabolites related to PV. Furthermore, the topological analysis of the MgADP-mediated sub-network revealed that IFNG, CD4, STAT3, IL-2, IL-1B, and JAK2 are hub-bottleneck proteins that play a significant role in Th17 cell differentiation.Conclusion: Th17 cell differentiation pathway, MgADP metabolite, and the IFNG, CD4, STAT3, IL2, IL-1B, and JAK2 were identified as significant factors involved. The connection between metabolic alterations and immune dysregulation was emphasized as a key mechanism in PV.