MicroRNA-204 attenuates oxidative stress damage of renal tubular epithelial cells in calcium oxalate kidney-stone formation via MUC4-mediated ERK signaling pathway.

Abstract

Oxalate-induced oxidative stress causes damage to cells, accompanied with renal deposition of calcium oxalate crystals. Recent studies have highlighted the extensive functions of microRNAs (miRNAs) in various processes, including cellular responses to oxidative stress. Hence, this study was intended to analyze the role of miR-204 in the calcium oxalate kidney-stone formation and the underlying mechanism. In silico analysis was performed to determine the miRNA/mRNA interaction involved in calculus, while dual-luciferase reporter assay was conducted for validation. A calcium oxalate kidney-stone model was established by H2O2 induction in RTEC HK-2 cells, in which the expression of miR-204 was examined. Gain- and loss-of-function approaches were employed to alter the expression of miR-204/MUC4 so as to assess the detailed role of miR-204 in oxidative stress injury in renal tubular epithelial cells (RTECs) and calcium oxalate kidney-stone formation. MUC4, an up-regulated gene in H2O2-induced HK-2 cells, was a target of MUC4. miR-204 functionally targeted MUC4 and blocked the ERK pathway activation. Furthermore, up-regulated miR-204 contributed to promotion of RTEC proliferation and suppression of ROS levels, RTEC apoptosis as well as formation of calcium oxalate crystal. Taken together, miR-204 impairs MUC4-dependent activation of the ERK signaling pathway and consequently ameliorates oxidative stress damage to RTECs and prevents calcium oxalate kidney-stone formation.

• Authors: Zhijuan Xie, Jianying Chen, Zhong Chen
• Journal: Urolithiasis (Urolithiasis) Vol. 50 Issue 1 Pg. 1-10 (Feb 2022) ISSN: 2194-7236 [Electronic] Germany
• PMID: 34783868 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• MicroRNAs
• Calcium Oxalate
• Hydrogen Peroxide

Topics

• Calcium Oxalate (metabolism)
• Epithelial Cells (metabolism)
• Humans
• Hydrogen Peroxide (metabolism, toxicity)
• Kidney (metabolism)
• MAP Kinase Signaling System
• MicroRNAs (genetics, metabolism)
• Oxidative Stress
• Signal Transduction