ABSTRACT
Steroid-resistant nephrotic syndrome (SRNS) is a clinical challenge with variable clinical outcomes. In patients with SRNS, unsuccessful anti-inflammatory and anti-proteinuric effects of steroids lead to end-stage renal disease (ESRD). Our objective was to define the expression pattern of the glucocorticoid receptors (GR) α and ß and their epigenetic regulators (miR-24, miR-30a, and miR-370) in a group of adults with SRNS. In this regard, sixty primary NS patients with focal segmental glomerulosclerosis (FSGS, N = 30) and membranous glomerulonephritis (MGN, N = 30) and also healthy volunteers (N = 24) were enrolled. Real-time PCR was performed to evaluate the expression levels of the aforementioned genes in peripheral blood mononuclear cell (PBMC) samples. Furthermore, an in-silico analysis was performed to understand the signaling pathways and biological procedures that may be targeted by these microRNAs in NS. The decreased and increased levels of GRα and GRß were not significant, respectively. Statistically significant reduced miR-24 levels were observed between control/MGN (p = .022) and MGN/FSGS (p = .032) groups. Additionally, a decrease was detected in miR-30a between MGN and FSGS (p = .049) groups. There was a significant increase in miR-370 expression level between control and NS groups (p = .029), as well as control/MGN (p = .008), and MGN/FSGS (p = .046). Bioinformatics analysis predicted the possible targets of the studied genes including genes involved in TGF-ß, Notch1, and p53 signaling pathways, regulation of gene expression, intracellular signal transduction, negative regulation of response to the stimulus, cell-cell signaling, and cell activation in the pathogenesis of SRNS. Taken all together, dysregulated levels of GRα, GRß were not attributed to SRNS in our patients. It seems that pharmacokinetics and the genetic variations in podocyte-related genes may be associated with the steroid-resistance in our adult patients with NS rather than GR expression.