CCL3 بهعنوان یک ژن کلیدی در مسیر سیگنالدهی کموکاین: بینشهایی از توالییابی RNA در درمان آرتریت پسوریاتیک
کد: G-1763
نویسندگان: Nima Ghasemi ℗, Hossein Azizi *, Melika Emarati
زمان بندی: زمان بندی نشده!
برچسب: آنالیز دادگان اومیکس
دانلود: دانلود پوستر
خلاصه مقاله:
خلاصه مقاله
Background and aims: Psoriatic arthritis is a chronic inflammatory disease characterized by the interplay of genetic, immune, and environmental factors, primarily affecting the joints and skin. Central to its pathogenesis is the dysregulated chemokine signaling pathway, which orchestrates the recruitment of immune cells to sites of inflammation. Chemokines such as CXCL10 and CCL2, along with their respective receptors (e.g., CXCR3 and CCR5), drive persistent inflammation, tissue damage, and joint destruction. This pathway not only contributes to the disease's clinical manifestations but also serves as a potential target for therapeutic interventions, highlighting its importance in understanding and managing PsA. Method: Bulk RNA sequencing data were retrieved from the GEO repository and analyzed using the GEO2R tool. Identified differentially expressed genes were employed to construct and study a protein-protein interaction network using the STRING database and Cytoscape software. Functional enrichment analysis was conducted via the Enrichr platform to explore the biological roles of key clusters. This method provides valuable insights into the molecular differences between healthy and psoriatic arthritis-affected skin, paving the way for potential therapeutic advancements. Results: Our analysis identified EGF, MMP9, MUC1, STAT1, CXCL8, and CXCL10 as the most central proteins among the differentially expressed genes. To uncover specific gene clusters driving distinct pathways, we utilized the Gephi application. Using its modularity algorithm, we identified five distinct functional protein clusters. Among these clusters, Cluster 2—comprising CCL3, FCGR3B, CCL4, FCGR3A, CD80, and CCR7—was identified as being associated with the chemokine signaling pathway through enrichment analysis. Within this cluster, CCL3 emerged as the most central gene based on metrics such as closeness, harmonic closeness, and eigenvector centrality. Notably, CCL3 was found to be connected with proteins such as GZMB, CD38, PLEK, CCR7, CD80, IL7R, CD28, FCGR3B, and CTLA4. Conclusion: Our analysis highlights critical molecular differences and key signaling pathways between healthy and psoriatic arthritis-affected skin. The identification of central proteins such as CCL3 and its connections within the chemokine signaling pathway provides insights into the pathophysiology of psoriatic arthritis. These findings could inform targeted therapeutic strategies and advance our understanding of inflammatory skin disorders.
کلمات کلیدی
Psoriatic Arthritis, Chemokine Signaling Pathway, RNA-sequencing