Expression of Glycogen Synthase Kinase 3ОІ in Nephrotic Syndrome

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Sepideh Zununi Vahed1, Elham Ahmadian2, Mohammadreza Ardalan3
1Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran, sepide.zununi@gmail.com
2Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran, ahmadian.elham@yahoo.com
3Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran, ardalan34@yahoo.com

Abstract Aberrant expression of glycogen synthase kinase-3 (GSK-3ОІ) in kidney cells has a harmful role in podocyte injury. In this work, we found that dysregulated levels of GSK-3ОІ may be involved in the pathogenesis of nephrotic syndrome, renal disease with proteinuria, with different etiology.

Keywords Nephrotic syndrome, Proteinuria, Membranous glomerulonephritis, Focal Segmental Glomerulosclerosis, GSK-3ОІ.

Motivation and aim

Motivation

Glycogen synthase kinase-3 (GSK-3) is a conserved multi-functional serine/threonine kinase that regulates various physiological processes, including gene expression, cell signaling [1], cellular proliferation, apoptosis, and intracellular communication. A detailed understanding of the GSK-3ОІ function and its expression in several pathological conditions will help the clinic manage different kidney diseases.

Aim.

Given the role of GSK-3ОІ in the podocytes injury [2,3], we evaluate its expression levels in PBMCs samples of patients with NS.

В Methods

The expression levels of GSK-3ОІ was evaluated in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS); MGN (membranous glomerulonephritis) and FSGS (focal segmental glomerulosclerosis) using real-time PCR. Sixty cases (30 FSGS and 30 MGN) were included based on the strict criteria. The results compared with healthy controls (n=24). The receiver operating characteristic (ROC) curve analysis was used for evaluating the potential of GSK-3ОІ in discriminating cases from controls.

Results

There were statistically significant increases in GSK-3ОІ expression level in NS (P=0.002) and FSGS (P<0.001) groups when compared to controls; however, it was not significant in the MGN group (P= 0.137). The GSK-3ОІ level was also significantly higher in the FSGS group in comparison to the MGN group. ROC curve analysis approved a diagnostic power of GSK-3ОІ in discriminating patients from healthy controls (AUC: 0.72, P= 0.002) with high sensitivity and specificity.

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