Purpose: To extend existing information of the transcriptome on human diabetic kidneys.
Methods: RNA sequencing was performed in kidney tissues from patients with biopsy-proven diabetes nephropathy (N=19) and healthy living kidney donors as controls (N=20).
Results: Principal Component Analysis showed a clear separation between glomerular and tubulointerstitial transcriptomic profiles. When comparing patient tissue with control tissue, DN patients displayed 1,550 and 4,530 differentially expressed genes in glomeruli and tubulointerstitium (adjusted p <0.01), respectively, compared to the living donors. Next, Gene Ontology and KEGG pathway analyses identified a glomerular enrichment of genes involved in inflammation and extracellular matrix organization, as well as a tubulointerstitial enrichment of genes involved in immunity and apoptosis. Several specific gene modules associated with renal function were revealed using a weighted gene co-expression network analysis.
Conclusions: The results show consistency with previous microarray findings but more importantly, also provide information on new transcripts associated with DN within the two compartments making up the functional unit (the nephron) responsible for glomerular filtration and reabsorption in the kidneys. Prominent disease-specific changes occur in both glomeruli and tubulointerstitium including relevant cellular processes such as reorganization of extracellular matrix and inflammation (glomeruli) well as apoptosis (tubulointerstitium). The results emphasize the potential of utilizing high-throughput transcriptomics to decipher new disease pathways and treatment targets in this high-risk patient population.
Download raw counts for glomerular compartment here
Download raw counts for tubulointerstitial compartment here