Integrative Informatics Analysis of Transcriptome and Identification of Interacted Genes in the Glomeruli and Tubules in CKD

Abstract

Chronic kidney disease (CKD) is a complex disease in which the renal function is compromised chronically. Many studies have indicated the crosstalk between the tubule and the glomerulus in CKD progression. However, our understanding of the interaction of tubular and glomerular injury remains incomplete. In this study, we applied a meta-analysis approach on the transcriptome of the tubules and glomeruli of CKD patients to identify differentially expressed genes (DEGs) signature. Functional analysis of pathways and Gene Ontology found that tubular DEGs were mainly involved in cell assembly and remodeling, glomerular DEGs in cell proliferation and apoptosis, and overlapping DEGs mainly in immune response. Correlation analysis was performed to identify the associated DEGs in the tubules and glomeruli. Secreted protein comparison and verification experiments indicated that WFDC2 from the tubule could downregulate PEX19 mRNA and protein levels at the glomeruli in diabetic kidney disease (DKD). This study revealed the distinctive pathways of the tubules and glomeruli and identified interacted genes during CKD progression.

CD8 T Cell‐Derived Exosomal miR‐186‐5p Elicits Renal Inflammation via Activating Tubular TLR7/8 Signal Axis

“…[ 48 ] Renal tubular injury may even occur earlier than glomerular dysfunction, [ 49 ] and cell injury molecules produced by damaged renal tubules may result in damage to glomeruli. [ 50 , 51 ] Tan et al. reported that mitigating renal tubular injury via reducing MMP‐7 expression provided significant protection against glomerular injury and proteinuria.…”

“…[48] Renal tubular injury may even occur earlier than glomerular dysfunction, [49] and cell injury molecules produced by damaged renal tubules may result in damage to glomeruli. [50,51] Tan et al reported that mitigating renal tubular injury via reducing MMP-7 expression provided significant protection against glomerular injury and proteinuria. [52] Through il-lustrating the effect of T cell exosomal miR-186-5p on activating renal tubular TLR7/8 signal axis and initiating renal inflammation and tissue damage, our results support the notion that renal tubular injury induced by T cell miR-186-5p can initiate or aggravate glomerular damage, and provide the miR-186-5p-TLR7/8 signal axis as a novel mechanism underlying T cell-mediated renal dysfunction.…”

Harnessing the Full Potential of Multi-Omic Analyses to Advance the Study and Treatment of Chronic Kidney Disease

“…A 2018 review summarised literature investigating transcriptomic analysis in the context of kidney disease (23), with a number of additional investigations published in recent years (146,(148)(149)(150)(151)(152)(153)(154)(155)(156)(157)(158)(159). An interesting study by Fan et al carried out RNA-seq analysis of kidney biopsies from early DKD, advanced DKD, or control patients, to reveal gene expression changes from healthy to disease states (158).…”