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01-04-2019 | Original Paper

Calcifying nanoparticles induce cytotoxicity mediated by ROS-JNK signaling pathways

Authors: Jihua Wu, Zhiwei Tao, Yaoliang Deng, Quan Liu, Yunlong Liu, Xiaofeng Guan, Xiang wang

Published in: Urolithiasis | Issue 2/2019

Abstract

Calcifying nanoparticles (CNPs) play an important role in kidney stone formation, but the mechanism(s) are unclear. CNPs were isolated and cultured from midstream urine of patients with kidney stones. CNP morphology and characteristics were examined by electron microscopy and electrophoresis analysis. Chemical composition was analyzed using energy-dispersive X-ray microanalysis and Western blotting. Human renal proximal convoluted tubule cell (HK-2) cultures were exposed to CNPs for 0, 12 and 72 h, and production of reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis levels were evaluated. CNPs isolated from patients showed classical morphology, the size range of CNPs were 15–500 nm and negative charge; they were found to contain fetuin-A. Exposure of HK-2 cells to CNPs induced ROS production, decreased mitochondrial membrane potential and decreased cell viability. Transmission electron microscopy showed that CNPs can enter the cell by phagocytosis, and micrographs revealed signs of apoptosis and autophagy. CNPs increased the proportion of apoptotic cells, down-regulated Bcl-2 expression and up-regulated Bax expression. CNPs also up-regulated expression of LC3-B, Beclin-1and p-JNK.CNPs are phagocytosed by HK-2 cells, leading to autophagy, apoptosis and ROS production, in part through activation of JNK signaling pathways. ROS and JNK pathways may contribute to CNP-induced cell injury and kidney stone formation.

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Title: Calcifying nanoparticles induce cytotoxicity mediated by ROS-JNK signaling pathways
Authors: Jihua Wu
Zhiwei Tao
Yaoliang Deng
Quan Liu
Yunlong Liu
Xiaofeng Guan
Xiang wang
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Published in: Urolithiasis / Issue 2/2019
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI: https://doi.org/10.1007/s00240-018-1048-8

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Calcifying nanoparticles induce cytotoxicity mediated by ROS-JNK signaling pathways

Abstract

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Abstract

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