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Application of metabolomics in urolithiasis: the discovery and usage of succinate

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized...

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Autores principales: Zhang, Xiu-zhen, Lei, Xiong-xin, Jiang, Yan-lin, Zhao, Long-mei, Zou, Chen-yu, Bai, Yun-jin, Li, Ya-xing, Wang, Rui, Li, Qian-jin, Chen, Qiu-zhu, Fan, Ming-hui, Song, Yu-ting, Zhang, Wen-qian, Zhang, Yi, Li-Ling, Jesse, Xie, Hui-qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867757/
https://www.ncbi.nlm.nih.gov/pubmed/36681678
http://dx.doi.org/10.1038/s41392-023-01311-z
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author Zhang, Xiu-zhen
Lei, Xiong-xin
Jiang, Yan-lin
Zhao, Long-mei
Zou, Chen-yu
Bai, Yun-jin
Li, Ya-xing
Wang, Rui
Li, Qian-jin
Chen, Qiu-zhu
Fan, Ming-hui
Song, Yu-ting
Zhang, Wen-qian
Zhang, Yi
Li-Ling, Jesse
Xie, Hui-qi
author_facet Zhang, Xiu-zhen
Lei, Xiong-xin
Jiang, Yan-lin
Zhao, Long-mei
Zou, Chen-yu
Bai, Yun-jin
Li, Ya-xing
Wang, Rui
Li, Qian-jin
Chen, Qiu-zhu
Fan, Ming-hui
Song, Yu-ting
Zhang, Wen-qian
Zhang, Yi
Li-Ling, Jesse
Xie, Hui-qi
author_sort Zhang, Xiu-zhen
collection PubMed
description Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones.
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spelling pubmed-98677572023-01-23 Application of metabolomics in urolithiasis: the discovery and usage of succinate Zhang, Xiu-zhen Lei, Xiong-xin Jiang, Yan-lin Zhao, Long-mei Zou, Chen-yu Bai, Yun-jin Li, Ya-xing Wang, Rui Li, Qian-jin Chen, Qiu-zhu Fan, Ming-hui Song, Yu-ting Zhang, Wen-qian Zhang, Yi Li-Ling, Jesse Xie, Hui-qi Signal Transduct Target Ther Article Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones. Nature Publishing Group UK 2023-01-21 /pmc/articles/PMC9867757/ /pubmed/36681678 http://dx.doi.org/10.1038/s41392-023-01311-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Xiu-zhen
Lei, Xiong-xin
Jiang, Yan-lin
Zhao, Long-mei
Zou, Chen-yu
Bai, Yun-jin
Li, Ya-xing
Wang, Rui
Li, Qian-jin
Chen, Qiu-zhu
Fan, Ming-hui
Song, Yu-ting
Zhang, Wen-qian
Zhang, Yi
Li-Ling, Jesse
Xie, Hui-qi
Application of metabolomics in urolithiasis: the discovery and usage of succinate
title Application of metabolomics in urolithiasis: the discovery and usage of succinate
title_full Application of metabolomics in urolithiasis: the discovery and usage of succinate
title_fullStr Application of metabolomics in urolithiasis: the discovery and usage of succinate
title_full_unstemmed Application of metabolomics in urolithiasis: the discovery and usage of succinate
title_short Application of metabolomics in urolithiasis: the discovery and usage of succinate
title_sort application of metabolomics in urolithiasis: the discovery and usage of succinate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867757/
https://www.ncbi.nlm.nih.gov/pubmed/36681678
http://dx.doi.org/10.1038/s41392-023-01311-z
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