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An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury

Renal fibrosis is the pathological repair reaction of the kidney to chronic injury, which is an important process of chronic kidney disease (CKD) progressing to end-stage renal failure. Nephrolithiasis is one of the most common renal diseases, with waist and abdomen pain, hematuria, urinary tract in...

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Autores principales: Gao, Songyan, Chao, Yufan, Li, Na, Li, Henghui, Zhao, Hongxia, Liu, Xinru, Chen, Wei, Dong, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927618/
https://www.ncbi.nlm.nih.gov/pubmed/35308536
http://dx.doi.org/10.3389/fmed.2022.805356
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author Gao, Songyan
Chao, Yufan
Li, Na
Li, Henghui
Zhao, Hongxia
Liu, Xinru
Chen, Wei
Dong, Xin
author_facet Gao, Songyan
Chao, Yufan
Li, Na
Li, Henghui
Zhao, Hongxia
Liu, Xinru
Chen, Wei
Dong, Xin
author_sort Gao, Songyan
collection PubMed
description Renal fibrosis is the pathological repair reaction of the kidney to chronic injury, which is an important process of chronic kidney disease (CKD) progressing to end-stage renal failure. Nephrolithiasis is one of the most common renal diseases, with waist and abdomen pain, hematuria, urinary tract infection, and other clinical symptoms, which can increase the risk of renal fibrosis. Oxalate crystal-induced kidney injury is an early stage of nephrolithiasis; it is of great significance to explore the mechanism for the prevention and treatment of nephrolithiasis. A rodent model of calcium oxalate (CaOx) crystal-induced kidney injury was used in the present study, and a network analysis method combining proteomics and metabolomics was conducted to reveal the mechanism of crystal kidney injury and to provide potential targets for the intervention of nephrolithiasis. Using the metabolomics method based on the UHPLC-Q/TOF-MS platform and the iTRAQ quantitative proteomics method, we screened a total of 244 metabolites and 886 proteins from the kidney tissues that had significant changes in the Crystal group compared with that in the Control group. Then, the ingenuity pathway analysis (IPA) was applied to construct a protein-to-metabolic regulatory network by correlating and integrating differential metabolites and proteins. The results showed that CaOx crystals could induce inflammatory reactions and oxidative stress through Akt, ERK1/2, and P38 MAPK pathways and affect amino acid metabolism and fatty acid β-oxidation to result in kidney injury, thus providing an important direction for the early prevention and treatment of nephrolithiasis.
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spelling pubmed-89276182022-03-18 An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury Gao, Songyan Chao, Yufan Li, Na Li, Henghui Zhao, Hongxia Liu, Xinru Chen, Wei Dong, Xin Front Med (Lausanne) Medicine Renal fibrosis is the pathological repair reaction of the kidney to chronic injury, which is an important process of chronic kidney disease (CKD) progressing to end-stage renal failure. Nephrolithiasis is one of the most common renal diseases, with waist and abdomen pain, hematuria, urinary tract infection, and other clinical symptoms, which can increase the risk of renal fibrosis. Oxalate crystal-induced kidney injury is an early stage of nephrolithiasis; it is of great significance to explore the mechanism for the prevention and treatment of nephrolithiasis. A rodent model of calcium oxalate (CaOx) crystal-induced kidney injury was used in the present study, and a network analysis method combining proteomics and metabolomics was conducted to reveal the mechanism of crystal kidney injury and to provide potential targets for the intervention of nephrolithiasis. Using the metabolomics method based on the UHPLC-Q/TOF-MS platform and the iTRAQ quantitative proteomics method, we screened a total of 244 metabolites and 886 proteins from the kidney tissues that had significant changes in the Crystal group compared with that in the Control group. Then, the ingenuity pathway analysis (IPA) was applied to construct a protein-to-metabolic regulatory network by correlating and integrating differential metabolites and proteins. The results showed that CaOx crystals could induce inflammatory reactions and oxidative stress through Akt, ERK1/2, and P38 MAPK pathways and affect amino acid metabolism and fatty acid β-oxidation to result in kidney injury, thus providing an important direction for the early prevention and treatment of nephrolithiasis. Frontiers Media S.A. 2022-03-03 /pmc/articles/PMC8927618/ /pubmed/35308536 http://dx.doi.org/10.3389/fmed.2022.805356 Text en Copyright © 2022 Gao, Chao, Li, Li, Zhao, Liu, Chen and Dong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Gao, Songyan
Chao, Yufan
Li, Na
Li, Henghui
Zhao, Hongxia
Liu, Xinru
Chen, Wei
Dong, Xin
An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury
title An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury
title_full An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury
title_fullStr An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury
title_full_unstemmed An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury
title_short An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury
title_sort integrated proteomics and metabolomics strategy for the mechanism of calcium oxalate crystal-induced kidney injury
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927618/
https://www.ncbi.nlm.nih.gov/pubmed/35308536
http://dx.doi.org/10.3389/fmed.2022.805356
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