Investigation of T cell-related hub genes in diabetic nephropathy by bioinformatics analysis and experiment validation

• Published in: Molecular immunology 2024-02, Vol.166, p.65-78
• Main Authors: Luo, Hongyan, Yang, Lirong, Ma, Danna, Bao, Xi, Zhang, Guoqing, Li, Bo, Cao, Shilu, Liu, Shunyao, Bao, Li, Jing E, Zheng, Yali
• Format: Article
• Language: English
• Subjects: bioinformatics; data collection; Diabetic nephropathy; gene expression regulation; Gene signature; genes; Immune cell infiltration; immune response; inflammation; kidneys; mice; microRNA; mortality; oxidative stress; risk factors; RNA-seq; T cells; T-lymphocytes; transcription (genetics); transcriptome
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2024.01.003

Diabetic nephropathy(DN) remains a significant risk factor for cardiovascular and all-cause mortality, and end-stage renal disease (ESRD) associated with it is growing in prevalence.However, there is absolutely no curative strategy for DN. We subjected db/db and control mouse kidneys to transcriptional sequencing analysis to obtain transcriptome expression profile data in the diabetic nephropathy.We next performed differential analysis of db/db and control mice kidney sequencing data to obtain differentially expressed genes. The differential expressed genes were intersected with the oxidative stress and inflammatory response related genes derived from the MGI/MsiDB gene set to yield oxidative stress inflammatory response related differential 122 genes (OIRDEGs). To further clarify the biological functions of DEGs, we conducted GOKEGG analysis and obtained the top 20 genes by five computational algorithms of the cytohubba plugin via cytoscape, respectively. The genes obtained by the five algorithms were intersected and the intersection genes were considered as key genes,including Cd40lg, Il2rb, Lck, Il2rg, Zap70, Serpinb1a. Also,we used GSEA and immune infiltration analysis to clarify the biological signaling pathways and immune cell infiltration that are substantial in the diabetic nephropathy.Correlation studies of key genes with immune cell infiltration revealed that they were correlated with the majority types of T cells while only with two types of B cells.Then, we predicted miRNA and TF for the key genes and constructed the interaction network. Finally, the expression differences of key genes were examined by validation dataset and RT-PCR experiment.In conclusion,we have identified key genes associated with T cell immune response in a diabetic nephropathy model, which bear significance in the etiopathogenesis of immunological injury in diabetic nephropathy and provide an innovative proposal for the recognition and management of DN. •Diabetic nephropathy is a major cause of end-stage renal disease.•Pathogenesis of diabetic nephropathy is undefined and key genes have essential contributions.•Key genes in diabetic nephropathy are associated with T cell development and signaling pathways.•T cell-associated immune-inflammatory responses may be a novel target for intervention in diabetic nephropathy.