Pharmacologically inhibiting glycogen synthase kinase-3β ameliorates renal inflammation and nephrotoxicity in an animal model of cisplatin-induced acute kidney injury

Hsing, Chung-Hsi and Tsai, Cheng-Chieh and Chen, Chia-Ling and Lin, Yu-Hui and Tseng, Po-Chun and Satria, Rahmat Dani and Lin, Chiou-Feng (2021) Pharmacologically inhibiting glycogen synthase kinase-3β ameliorates renal inflammation and nephrotoxicity in an animal model of cisplatin-induced acute kidney injury. Biomedicines, 9 (8). ISSN 22279059

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Abstract

The adverse effect of cisplatin administration causes acute kidney injury (AKI) following renal inflammation and nephrotoxicity, characterized by proximal tubular cell apoptosis and necrosis. Pro-apoptotic and pro-inflammatory roles of glycogen synthase kinase (GSK)-3β have been reported. This study investigated the therapeutic blockade of GSK-3β in cisplatin-induced AKI. A renal cisplatin nephrotoxicity model showed activation of GSK-3β in vivo, particularly in proximal tubular epithelial cells. Pharmacologically inhibiting GSK-3β abolished cisplatin nephrotoxicity, including proximal tubular injury, cell cytotoxicity, and biochemical dysfunction. Additionally, GSK-3β inhibitor treatment ameliorated renal inflammation by reducing immune cell infiltration, cell adhesion molecule expression, and pro-inflammatory cytokine/chemokine production. Cisplatin treatment caused GSK-3β activation in vitro in the human renal proximal tubular epithelial cell line HK-2, whereas either pharmacological administration of GSK-3β inhibitors or genetic transduction of GSK-3β short-hairpin RNA impeded cisplatin-induced cytotoxicity. These results indicate that cisplatin activates GSK-3β followed by GSK-3β-mediated renal inflammation and nephrotoxicity, contributing to AKI. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Additional Information: Cited by: 6; All Open Access, Gold Open Access
Uncontrolled Keywords: cisplatin; AKI; GSK-3β; renal inflammation; nephrotoxicity
Subjects: R Medicine > RB Pathology
Divisions: Faculty of Medicine, Public Health and Nursing > Biomedical Sciences
Depositing User: Sri JUNANDI
Date Deposited: 26 Sep 2024 07:34
Last Modified: 26 Sep 2024 07:34
URI: https://ir.lib.ugm.ac.id/id/eprint/4616

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