Dysregulated levels of glycogen synthase kinase-3β (GSK-3β) and miR-135 in peripheral blood samples of cases with nephrotic syndrome

Mohammadreza Ardalan; Seyyedeh Mina Hejazian; Hassan Fazlazar Sharabiyani; Farahnoosh Farnood; Amirhossein Ghafari Aghdam; Milad Bastami; Elham Ahmadian; Sepideh Zununi Vahed; Magali Cucchiarini

doi:10.7717/peerj.10377

Dysregulated levels of glycogen synthase kinase-3β (GSK-3β) and miR-135 in peripheral blood samples of cases with nephrotic syndrome

PeerJ. 2020 Dec 16:8:e10377. doi: 10.7717/peerj.10377. eCollection 2020.

Affiliations

¹ Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
² Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
³ Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
⁴ Center of Experimental Orthopaedics, Universität des Saarlandes, Homburg/Saar, Germany.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Focal Segmental Glomerulosclerosis; GSK-3β; Membranous glomerulonephritis; Nephrotic syndrome; Proteinuria; miR-135a-5p.

Grants and funding

This work was financially supported by the Kidney Research Center, Tabriz University of Medical Sciences and a Research Grant (Grant No. 62640). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.