Gene alterations in monocytes are pathogenic factors for immunoglobulin a nephropathy by bioinformatics analysis of microarray data

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.

Histone deacetylase 10, a potential epigenetic target for therapy

“…HDAC10 is also a latent biomarker in immunoglobulin A nephropathy (IgAN) and renal fibrosis as well [ 111 , 112 ]. HDAC10 protein levels are significantly higher in fibrotic kidneys.…”

“…However, piceatannol treatment does not diminish HDAC10 expression but the results hint that HDAC10 may regulate renal fibrosis via other signaling pathways [ 111 ]. To determine a biomarker for IgAN, Guo et al [ 112 ] utilized samples from the Gene Expression Omnibus (GEO) database and found that HDAC10 existed in monocytes of IgAN samples, which enriches in both alcoholism and chromatin modifying enzymes via construction of functional interaction (FI) network.…”

Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy

“…Previous two studies have suggested that the decrease in number and function of NK cells were associated with the disease progression of IgAN [ 31 , 32 ]. Altered monocyte gene expression patterns and numbers were found to be pathogenic factors in IgAN [ 33 , 34 ]. Higher respiratory burst and metabolic reprogramming in monocytes have been linked to the pathogenesis of IgAN [ 30 , 35 ].…”

“…In particular, the elevated expression of NDUFS3 and TNFRSF1A suggested the altered mitochondrial respiratory function and death receptor homeostasis in monocytes. Intriguingly, two recent studies have confirmed that TNF gene expression levels in monocytes from IgAN patients are reduced compared with those from healthy donors [ 30 , 34 ], further suggesting a reduced TNF alpha signaling pathway in IgAN patients. In our scRNA-seq results, we find a classical monocyte subset is slightly increased in IgAN.…”