A Partial Picture of the Single-Cell Transcriptomics of Human IgA Nephropathy

Abstract

The molecular mechanisms underlying renal damage of IgA nephropathy (IgAN) remain incompletely defined. Here, single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from IgAN and control subjects to define the transcriptomic landscape at single-cell resolution. We presented a comprehensive scRNA-seq analysis of human renal biopsies from IgAN. We showed for the first time that IgAN mesangial cells displayed increased expression of several novel genes including MALAT1, GADD45B, SOX4, and EDIL3, which were related to cell proliferation and matrix accumulation. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. Furthermore, we compared the results of 4 IgAN patients with the published scRNA-Seq data of healthy kidney tissues of three human donors in order to further validate the findings in our study. The results also verified that the overexpressed genes in tubule cells from IgAN patients were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. The receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. IgAN patients with overt proteinuria displayed elevated genes participating in several signaling pathways compared with microproteinuria group. It needs to be mentioned that based on number of mesangial cells and other kidney cells analyzed in this study, the results of our study are preliminary and needs to be confirmed on larger number of cells from larger number of patients and controls in future studies. Therefore, these results offer new insight into pathogenesis and identify new therapeutic targets for IgAN.

The Diagnostic and Predictive Significance of Immune-Related Genes and Immune Characteristics in the Occurrence and Progression of IgA Nephropathy

“…The TFRC gene involved in ferroptosis and some other important pathogenesis has been linked to a variety of diseases [ 46 ] and may be linked to IgAN susceptibility; meanwhile, NEAT1, MALAT1, and XIST which have the most degree with miRNA in the ceRNA network were identified; NEAT1 may affect IgAN by regulating the TLR2/NF- κ B signaling pathway [ 47 ]. Besides, research once showed that IgAN mesangial cells displayed increased expression of MALAT1 [ 48 ], and XIST could mediate inflammatory response via NF- κ B/NLRP3 inflammasome pathway, which may be the potential pathomechanism by which it affects the IgAN progression.…”

The Signaling Pathway of TNF Receptors: Linking Animal Models of Renal Disease to Human CKD

“…Accordingly, Ihara et al showed that a profile of multiple circulating TNF receptors, including TNFR1 and TNFR2, was associated with early progressive renal decline in type 1 diabetes [ 137 ]. Tubular cells of IgA nephropathy patients also overexpressed genes of the inflammatory TNF signaling pathway [ 138 ].…”

The molecular mechanisms of inflammation and scarring in the kidneys of immunoglobulin A nephropathy

“…Tang et al [ 28 ] conducted another RNA-seq study at the single-cell level. They identified DEGs in mesangial cells, endothelial cells, podocytes and tubular cells (Table 2 ).…”