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Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro

Accumulating evidence suggests that autophagy is involved in the pathophysiological processes of kidney diseases. However, the role of autophagy in the formation of calcium oxalate (CaOx) nephrolithiasis remains unclear. In this study, we investigated the effects of autophagy on renal tubular epithe...

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Autores principales: Liu, Yunlong, Li, Derong, He, Ziqi, Liu, Quan, Wu, Jihua, Guan, Xiaofeng, Tao, Zhiwei, Deng, Yaoliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796996/
https://www.ncbi.nlm.nih.gov/pubmed/29435125
http://dx.doi.org/10.18632/oncotarget.23383
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author Liu, Yunlong
Li, Derong
He, Ziqi
Liu, Quan
Wu, Jihua
Guan, Xiaofeng
Tao, Zhiwei
Deng, Yaoliang
author_facet Liu, Yunlong
Li, Derong
He, Ziqi
Liu, Quan
Wu, Jihua
Guan, Xiaofeng
Tao, Zhiwei
Deng, Yaoliang
author_sort Liu, Yunlong
collection PubMed
description Accumulating evidence suggests that autophagy is involved in the pathophysiological processes of kidney diseases. However, the role of autophagy in the formation of calcium oxalate (CaOx) nephrolithiasis remains unclear. In this study, we investigated the effects of autophagy on renal tubular epithelial cell injury induced by CaOx crystals in vivo and in vitro. We first observed that the expression levels of LC3-II and BECN1 and number of autophagic vacuoles were markedly increased in the renal tissue of CaOx stone patients. We subsequently found that exposure of HK-2 cells to CaOx crystals could increase LC3-II and BECN1 expression as well as the number of GFP-LC3 dots and autophagic vacuoles in a dose- and time-dependent manner. In addition, our results suggest that CaOx crystals induced autophagy, at least in part, via activation of the reactive oxygen species (ROS) pathway in HK-2 cells. Furthermore, inhibition of autophagy using 3-methyladenine or siRNA knockdown of BECN1 attenuated CaOx crystal-induced HK-2 cells injury. However, enhancing autophagic activity with rapamycin exerted an opposite effect. Taken together, our results demonstrate that autophagy is essential for CaOx crystal-induced renal tubular epithelial cell injury and that inhibition of autophagy could be a novel therapeutic strategy for CaOx nephrolithiasis.
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spelling pubmed-57969962018-02-12 Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro Liu, Yunlong Li, Derong He, Ziqi Liu, Quan Wu, Jihua Guan, Xiaofeng Tao, Zhiwei Deng, Yaoliang Oncotarget Research Paper Accumulating evidence suggests that autophagy is involved in the pathophysiological processes of kidney diseases. However, the role of autophagy in the formation of calcium oxalate (CaOx) nephrolithiasis remains unclear. In this study, we investigated the effects of autophagy on renal tubular epithelial cell injury induced by CaOx crystals in vivo and in vitro. We first observed that the expression levels of LC3-II and BECN1 and number of autophagic vacuoles were markedly increased in the renal tissue of CaOx stone patients. We subsequently found that exposure of HK-2 cells to CaOx crystals could increase LC3-II and BECN1 expression as well as the number of GFP-LC3 dots and autophagic vacuoles in a dose- and time-dependent manner. In addition, our results suggest that CaOx crystals induced autophagy, at least in part, via activation of the reactive oxygen species (ROS) pathway in HK-2 cells. Furthermore, inhibition of autophagy using 3-methyladenine or siRNA knockdown of BECN1 attenuated CaOx crystal-induced HK-2 cells injury. However, enhancing autophagic activity with rapamycin exerted an opposite effect. Taken together, our results demonstrate that autophagy is essential for CaOx crystal-induced renal tubular epithelial cell injury and that inhibition of autophagy could be a novel therapeutic strategy for CaOx nephrolithiasis. Impact Journals LLC 2017-12-17 /pmc/articles/PMC5796996/ /pubmed/29435125 http://dx.doi.org/10.18632/oncotarget.23383 Text en Copyright: © 2018 Liu et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Liu, Yunlong
Li, Derong
He, Ziqi
Liu, Quan
Wu, Jihua
Guan, Xiaofeng
Tao, Zhiwei
Deng, Yaoliang
Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
title Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
title_full Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
title_fullStr Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
title_full_unstemmed Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
title_short Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
title_sort inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796996/
https://www.ncbi.nlm.nih.gov/pubmed/29435125
http://dx.doi.org/10.18632/oncotarget.23383
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