Authors : Panigrahi S, Pardeshi VC, Chandrasekaran K, Neelakandan K, Ps H, Vasudevan A
Publication Year : 2020
BACKGROUND:
Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity.
PURPOSE:
This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes.
METHODS:
Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroid-sensitive nephrotic syndrome [SSNS], n = 4; steroid-resistant nephrotic syndrome [SRNS], n = 2; and healthy adult individuals [control], n = 2) were generated using microarray analysis.
RESULTS:
Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene [removed]DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 upregulated, 47 downregulated) in SSNS and 139 genes (78 upregulated, 61 downregulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (p less than or equal to 0.05, -1 less than or equal to log2 FC greater than or equal to 1) differentially expressed genes identified the transforming growth factor-ß and JAK-STAT pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2350 genes with values of p less than or equal to 0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS.
CONCLUSION:
Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.