Co-regulatory Network of RNA-Binding Proteins and Alternative Splicing in the Pathogenesis of Lupus Nephritis

Lupus nephritis (LN), the most severe complication of systemic lupus erythematosus (SLE), remains incompletely understood at the molecular level. This study systematically investigates the regulatory roles and immune relevance of RNA-binding proteins (RBPs) and alternative splicing (AS) in LN through integrated bioinformatics analysis and experimental validation. Utilizing RNA sequencing data from public datasets, SUVA-based AS analysis, and DESeq2 differential expression analysis, we identified 317 upregulated and 313 downregulated genes in renal tissues of LN patients. Among these, 27 differentially expressed RBPs were significantly associated with immune response pathways. Further analysis revealed that 25 immune-related alternative splicing events formed a co-expression regulatory network with 18 RBPs. Functional enrichment and GSEA demonstrated significant activation of interferon signaling pathways and suppression of TNF α/NF-κB pathways in LN. The differential expression of RBPs and pathways related genes, as well as the splicing ratio changes of AS-related genes were validated in human specimens via RT-qPCR. This study is the first to elucidate the co-regulatory network of RBPs and AS in the pathogenesis of LN, providing a theoretical foundation for precision therapeutic strategies targeting post-transcriptional regulation.