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 β 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 GRβ 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‐β, 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, GRβ 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.

中文翻译：

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类固醇抵抗性肾病综合征成人的糖皮质激素受体及其上游表观遗传调节因子

类固醇耐药性肾病综合征 (SRNS) 是一项临床挑战，临床结果各不相同。在 SRNS 患者中，类固醇的抗炎和抗蛋白尿作用不成功会导致终末期肾病 (ESRD)。我们的目标是确定一组 SRNS 成人中糖皮质激素受体 (GR) α 和 β 及其表观遗传调节因子（miR-24、miR-30a 和 miR-370）的表达模式。在这方面，60 名患有局灶节段性肾小球硬化（FSGS，N  = 30）和膜性肾小球肾炎（MGN，N  = 30）的原发性 NS 患者以及健康志愿者（N = 24) 被录取。进行实时 PCR 以评估上述基因在外周血单核细胞 (PBMC) 样本中的表达水平。此外，还进行了计算机分析，以了解 NS 中这些 microRNA 可能靶向的信号通路和生物学过程。GRα 和 GRβ 水平的降低和升高分别不显着。在对照/MGN ( p  = .022) 和 MGN/FSGS ( p  = .032) 组之间观察到统计学上显着降低的 miR-24 水平。此外，在 MGN 和 FSGS ( p  = .049) 组之间检测到 miR-30a 的减少。miR-370 表达水平在对照组和 NS 组之间显着增加（p = 0.029），以及控制/ MGN（p  = 0.008），和MGN / FSGS（p  = 0.046）。生物信息学分析预测了研究基因的可能靶点，包括参与 TGF-β、Notch1 和 p53 信号通路的基因、基因表达的调节、细胞内信号转导、对刺激反应的负调节、细胞间信号传导和细胞活化在 SRNS 的发病机制中。总之，GRα、GRβ 的失调水平不归因于我们患者的 SRNS。似乎足细胞相关基因的药代动力学和遗传变异可能与我们成年 NS 患者的类固醇抗性有关，而不是 GR 表达。