Disrupting circ-GNB4 mitigates high glucose-induced human mesangial cells injury by regulating the proliferation, ECM accumulation, inflammation and oxidative stress through circ-GNB4/miR-23c/EGR1 pathway [RETRACTED].

Abstract

ABSTRACT:

Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. Although G protein subunit beta 4 (GNB4)-derived circular RNA (circ-GNB4; hsa_circ_0068087) is a promising candidate biomarker in diabetes mellitus, whether circ-GNB4 participates in DN occurrence and development remains unknown. Herein, we focused on DN-associated human renal mesangial cells (HRMCs) injury, and HRMCs were exposed in high glucose (HG) condition. Using quantitative polymerase chain reaction and western blotting, we found that circ-GNB4 and early growth response factor 1 (EGR1) were upregulated, whereas microRNA (miR)-23c was downregulated in DN patients' sera and HG-stimulated HRMCs. HG-induced injuries were measured by MTS method, western blotting, enzyme-linked immunosorbent assay and other special assay kits. Consequently, HG could inhibit superoxide dismutase activity, but induce cell proliferation and levels of malondialdehyde, Fibronectin, Collagen I, Collagen IV, interleukin-6, interleukin-1β, and tumor necrosis factor-α. However, HG-induced these injuries were overall suppressed by silencing circ-GNB4 or overexpressing miR-23c. Moreover, miR-23c knockdown could counteract the effect of circ-GNB4 deficiency, and EGR1 restoration abrogated miR-23c overexpression role in HG-stimulated HRMCs. Notably, circ-GNB4 could target miR-23c and EGR1 was targeted by miR-23c, as confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. Moreover, EGR1 expression was positively modulated by circ-GNB4 via miR-23c. Collectively, circ-GNB4 might be a novel mechanism of DN-induced HRMCs injury, and there was a circ-GNB4/miR-23c/EGR1 pathway underlying the proliferation, extracellular matrix accumulation, inflammation and oxidative stress. This study suggested circ-GNB4 as a potential target to interfere the development of DN.

• Authors: Jing Chang, Zhan Fang, Dan Wang, Haiyan He, Fang Sun, Jian Teng, Lina Yang
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) (Aug 19 2022) ISSN: 1533-4023 [Electronic] United States
• PMID: 35170486 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.