Abstract
BackgroundImmunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulopathy worldwide. The study aimed to provide potential molecular biomarkers for IgAN management.MethodsThe public gene expression profiling GSE58539 was utilized, which contained 17 monocytes samples (8 monocytes samples isolated from IgAN patients and 9 monocytes samples isolated from healthy blood donors). Firstly, differentially expressed genes (DEGs) between the two kinds of samples were identified by limma package. Afterwards, pathway enrichment analysis was implemented. Thereafter, protein-protein interaction (PPI) network was constructed and key nodes in PPI network were predicted using four network centrality analyses. Ultimately, gene functional interaction (FI) was constructed according to expressions in each sample, and then module network was extracted from FI network.ResultsA total of 678 DEGs were screened out, of these, 72 DEGs were identified as crucial nodes in PPI network that could well distinguish IgAN and healthy samples. In particular, IL6, TNF, IL1B, PRKACA and CCL20 were closely related to pathways such as hematopoietic cell lineage, apoptosis and Toll-like receptor (TLR) signaling pathway. Moreover, 12 genes in the FI network belonged to the 72 identified key nodes, such as CCL20, HDAC10, FPR2 and PRKACA, which were also key genes in 4 module networks.ConclusionsSeveral crucial genes were identified in monocytes of IgAN patients, such as IL6, TNF, IL1B, CCL20, PRKACA, FPR2 and HDAC10. These genes might co-involve in pathways such as TLR and apoptosis signaling during IgAN progression.
Highlights
Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulopathy worldwide
A total of 72 genes were identified that could well distinguish IgAN and healthy samples (Fig. 3). Genes such as IL6, tumor necrosis factor (TNF), IL1B, PRKACA, TYK2 and C motif chemokine ligand 20 (CCL20) were closely related to five the pathways, including NOD-like receptor signaling pathway, cytokine-cytokine receptor interaction, hematopoietic cell lineage, apoptosis, and Toll-like receptor signaling pathway (Table 2)
12 genes in the functional interaction (FI) network belonged to the 72 identified key nodes, such as CCL20, histone deacetylase 10 (HDAC10), formyl peptide receptor 2 (FPR2) and PRKACA
Summary
Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulopathy worldwide. The study aimed to provide potential molecular biomarkers for IgAN management. Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulopathy. 20–50% of adults who suffered with IgAN would progress to end-stage renal diseases [1]. It is pivotal for IgAN patients to identify predictors of prognosis. Numerous risk factors associated with IgAN progression have. Several biomarkers have been identified, such as levels of urinary secretory (sIgA) [8], serum galactose-deficient immunoglobulin A1 (Gd-IgA1) [9] and the tandem repeats polymorphism of MUC20 gene [10]. Cellular events involved in the IgAN pathogenesis are unclear
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