Oxalate-upregulated annexin A6 promotes the formation of calcium oxalate kidney stones by exacerbating calcium release-mediated oxidative stress injury in renal tubular epithelial cells and crystal-cell adhesion.

Autor: Xiao F; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 443002, Hubei Province, China., Guan Y; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 443002, Hubei Province, China., Liu T; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 443002, Hubei Province, China., Zeng Y; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 443002, Hubei Province, China., Zhu H; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 443002, Hubei Province, China. Electronic address: zhcheng2018@outlook.com., Yang K; Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 443002, Hubei Province, China. Electronic address: kangyang@whu.edu.cn.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 Nov; Vol. 761, pp. 110187. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1016/j.abb.2024.110187
Abstrakt: Kidney stones result from abnormal biomineralization, although the mechanism behind their formation remains unclear. Annexin A6 (AnxA6), a calcium-dependent lipid-binding protein, is associated with several mineralization-related diseases, but its role in kidney stones is unknown. This study aimed to explore the role and mechanism of AnxA6 in calcium oxalate (CaOx) kidney stones. An in vitro model in which renal tubular epithelial cells (RTECs) were treated with 1 mmol/L oxalate was established, and AnxA6 protein and mRNA expression were examined. Genetic engineering, drug intervention, and biochemical assays were used to investigate the role of AnxA6. The results revealed that AnxA6 was significantly overexpressed in the CaOx model. AnxA6 knockdown in RTECs reduced oxalate-induced oxidative stress, ROS accumulation, and mitochondrial damage, whereas AnxA6 overexpression exacerbated these effects. Blocking ryanodine receptor-mediated calcium release reversed AnxA6-induced oxidative damage. Additionally, AnxA6 increased oxalate adhesion to RTECs by binding to oxalate. In conclusion, AnxA6 contributes to CaOx kidney stone formation by promoting both oxidative stress via calcium release and crystal-cell adhesion by binding to oxalate. This study offers new insight into CaOx kidney stone formation.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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