Identification of key genes and regulatory mechanisms in Lupus nephritis pathogenesis

Lupus nephritis (LN), one of the main causes of end stage renal disease and mortality, is an autoimmune disease with the usual hallmark of glomerulonephritis . Glomerular repositioning of immune complexes, and T and B cells overactivation are both involved in the LN pathogenicity . The aim of the present study was to investigate key drivers of LN pathogenesis by analyzing a related expression profile (GSE۱۱۲۹۴۳) to discover some potential drug targets for this malignancy. Firstly, dataset quality check was performed by principal component analysis, and control and disease samples were perfectly separated. Using Linear Model for Microarray Analysis (Limma) algorithm, ۷۵۳۲ differentially expressed genes were identified. Next, the differentially expressed genes were subjected to Gene Ontology and Reactome pathway enrichment analyses to explore the disease related regulatory mechanisms. MAPK cascade, Neutrophil activation involved in immune system, Neutrophil degranulation, and immune system were among the top enriched terms. These results were in line with previous studies on the immune system deficiency in LN patients. Furthermore, a protein-protein interaction network was constructed, and top genes were selected based on their degree of centrality. In parallel, weighted gene co-expression network analysis (WGCNA) algorithm clustered the co-expressed genes into ۱۳ distinct modules, and the blue module was selected as disease most correlated module. To improve reliability in hub gene selection, we explored the top genes spotted by the network analysis and WGCNA. As a result, ۸ hub genes including EP۳۰۰, ITGAV, NUP۱۵۳, VES ۱, RAF۱, MAP۲K۱, HIF۱A, and SIRT۱ were identified as key players in LN pathogenesis. Using an integrative approach, this study nominated some of the main drivers of this complex disease which could be validated through wet lab trials to reach potential drug targets.

کلیدواژه ها:

Lupus nephritis ، WGCNA ، Therapeutic target ، Hub genes