Kidney Transcriptomic and Proteomic Analyses Provide New Insight into the Pathogenesis of IgA Nephropathy in Mice.

Abstract

Immunoglobulin A nephropathy (IgAN) is a common clinically refractory disease and is a significant cause of end-stage renal failure. However, its pathogenesis remains unclear. Studying the pathogenesis is of great significance for the development of clinical interventions and the identification of diagnostic markers. An IgAN mouse model was established through oral administration of bovine serum albumin, subcutaneous injection of carbon tetrachloride, and tail vein injection of lipopolysaccharide. Transcriptome sequencing and TMT protein sequencing were employed to analyze the mRNA and protein expression profiles in the kidney tissue of IgAN mice. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted on differentially expressed genes (DEGs) and proteins (DEPs). A protein-protein interaction (PPI) network diagram was constructed for overexpressed genes and proteins to identify hub DEGs and DEPs. Additionally, the correlation between core genes and proteins and the glomerular filtration rate was examined using the Nephroseq v5 database. The serum biochemical indicators and renal tissue pathology tests confirmed the successful construction of the IgAN mouse model. A total of 415 DEGs were identified through transcriptome sequencing, while 99 DEPs were obtained via TMT protein sequencing. The intersection of these datasets yielded 21 co-expressed DEGs/DEPs. Functional enrichment analysis revealed significant enrichment in signaling pathways related to inflammatory response, immune regulation, amino acid metabolism, and lipid metabolism. Additionally, LCN2, HMGCR, and HDC were identified as the key hub DEGs/DEPs within the PPI network. Clinical correlation analysis demonstrated a clear relationship between LCN2, HMGCR, HDC, and glomerular filtration rate. This study offers new insights into the pathogenesis of IgAN and presents potential novel diagnostic and therapeutic targets.