Identification of potential biomarkers and therapeutic targets for human IgA nephropathy and hypertensive nephropathy by bioinformatics analysis

Abstract

In order to further elucidate the potential correlations and treatments of IgA nephropathy (IgAN) and hypertensive nephropathy (HT), bioinformatics analysis of IgAN and HT was performed. The mRNA expression profiles of human renal biopsy samples from patients with IgAN, patients with HT and pre-transplant healthy living controls (LD) were downloaded from the Gene Expression Omnibus database. Then, the differentially expressed genes (DEGs) were identified and functions of DEGs were analyzed. Finally, the regulatory networks containing DEGs and related-transcription factors (TFs) were constructed using Cytoscape software. When compared with the LD group, 134 and 188 DEGs were obtained in the IgAN and HT groups, respectively. A total of 39 genes were altered in the HT group when compared with the IgAN group. In addition, 66 genes were shared in the IgAN and HT groups when compared with the LD group, 6 of which [early growth response 1, activating transcription factor 3, nuclear receptor subfamily 4 group A member 2 (NR4A2), NR4A1, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F and Kruppel like factor 6] were identified as TFs. In addition, DEGs including interleukin (IL) 1 receptor antagonist, collagen type 4 α2 chain, IL8, FBJ murine osteosarcoma viral oncogene homolog and somatostatin were enriched in a number of inflammation-associated biological processes, and DEGs including structural maintenance of chromosomes protein 3, v-crk avian sarcoma virus CT10 oncogene homolog and myosin 6 were enriched in non-inflammation-associated biological processes. Therefore, the differentially expressed TF genes and the genes associated with inflammation may be effective as potential therapeutic targets for IgAN and HT.

Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents

“…Re-analyzing and integration of omics-based expression profiles could be an advantageous tactic to catch a holistic view of the involving genes and miRNAs in the IgAN pathogenesis. Until now, several re-analyzes have been performed on the IgAN related expression profiles, mostly on kidney tissue samples of the patients [25][26][27][28].…”

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

“…To fully explain kidney damage in IgAN, it is necessary to fully understand the effects of TLR4 in the development of glomerulopathy, involving both glomerular cells and circulating leukocytes. Studies have shown that the administration of LPS activates TLR4 receptors on mesangial cells, and causes the release of chemokines (CXCs), which promotes neutrophil infusion and the development of glomerulonephritis [114][115][116]. In addition, the IFN-γ and IFN-α responses induced by TLR activation induce overexpression of the B-cell activation factor (BAFF) in dendritic cells, favoring the expansion of B-cells and increasing IgA synthesis [117][118][119][120][121].…”

Comprehensive Analysis of IgA Nephropathy Expression Profiles: Identification of Potential Biomarkers and Therapeutic Agents

“…Re-analyzing and integration of omics-based expression pro les could be an advantageous tactic to catch a holistic view of the involving genes and miRNAs in the IgAN pathogenesis. Until now, several reanalyzes have been performed on the IgAN related expression pro les, mostly on kidney tissue samples of the patients [25][26][27][28]. As far as we know, there are just one experiment conducting a meta-analysis study seeking for DEGs in the PBMCs of IgAN patients.…”