Dysregulated levels of glycogen synthase kinase-3β (GSK-3β) and miR-135 in peripheral blood samples of cases with nephrotic syndrome.
Dysregulated levels of glycogen synthase kinase-3β (GSK-3β) and miR-135 in peripheral blood samples of cases with nephrotic syndrome.
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DOI：
10.7717/peerj.10377
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发表时间：
2020
期刊：
影响因子：
2.7
通讯作者：
Cucchiarini M
中科院分区：
文献类型：
--
作者：
Ardalan M;Hejazian SM;Sharabiyani HF;Farnood F;Ghafari Aghdam A;Bastami M;Ahmadian E;Zununi Vahed S;Cucchiarini M
糖原合成酶激酶-3（Glycogen synthase kinase-3，GSK-3 β）是一种丝氨酸/苏氨酸激酶，在多种生理过程中具有多种功能。GSK-3 β在肾细胞中的异常水平在足细胞损伤中具有有害作用。在这篇文章中，GSK-3 β及其上游调节因子之一miR-135a-5p在最常见类型的肾病综合征（NS）、局灶节段性肾小球硬化（FSGS）和膜性肾小球肾炎（MGN）病例的外周血单个核细胞（PBMC）中的表达水平被测量。在这样做的过程中，52例沿着与24名健康对照者被包括在严格的标准的基础上。采用实时荧光定量PCR检测GSK-3 β mRNA和miR-135水平。与对照组相比，NS组（P = 0.001）、MGN组（P = 0.002）和FSGS组（P = 0.015）中GSK-3 β表达水平均显著升高。PBMC中miR-135a-5p的失调水平在研究组之间不显著。此外，与对照组相比，NS（P = 0.020）、MGN（P = 0.040）和FSGS（P = 0.046）患者血浆中miR-135a-5p的表达水平显著降低。ROC曲线分析证实GSK-3 β在区分患者和健康对照者方面具有较高的敏感性和特异性（AUC：0.72，P = 0.002）。GSK-3 β及其调节因子miR-135a的表达异常可能参与了不同病因的NS的发病机制。因此，需要更多的研究来了解它们之间的关系。
Glycogen synthase kinase-3 (GSK-3β) is a serine/threonine kinase with multifunctions in various physiological procedures. Aberrant level of GSK-3β in kidney cells has a harmful role in podocyte injury. In this article, the expression levels of GSK-3β and one of its upstream regulators, miR-135a-5p, were measured in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS); focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). In so doing, fifty-two cases along with twenty-four healthy controls were included based on the strict criteria. Levels of GSK-3β mRNA and miR-135 were measured with quantitative real-time PCR. There were statistically significant increases in GSK-3β expression level in NS (P = 0.001), MGN (P = 0.002), and FSGS (P = 0.015) groups compared to the control group. Dysregulated levels of miR-135a-5p in PBMCs was not significant between the studied groups. Moreover, a significant decrease was observed in the expression level of miR-135a-5p in the plasma of patients with NS (P = 0.020), MGN (P = 0.040), and FSGS (P = 0.046) compared to the control group. ROC curve analysis approved a diagnostic power of GSK-3β in discriminating patients from healthy controls (AUC: 0.72, P = 0.002) with high sensitivity and specificity. Dysregulated levels of GSK-3β and its regulator miR-135a may participate in the pathogenesis of NS with different etiology. Therefore, more research is needed for understanding the relationship between them.