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Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation

Escherichia coli (E. coli) is closely associated with the formation of kidney stones. However, the role of E. coli in CaOx stone formation is not well understood. We explored whether E. coli facilitate CaOx stone formation and its mechanism. Stone and urine cultures were reviewed from kidney stone f...

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Autores principales: An, Lingyue, Wu, Weizhou, Li, Shujue, Lai, Yongchang, Chen, Dong, He, Zhican, Chang, Zhenglin, Xu, Peng, Huang, Yapeng, Lei, Min, Jiang, Zheng, Zeng, Tao, Sun, Xinyuan, Sun, Xuan, Duan, Xiaolu, Wu, Wenqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292073/
https://www.ncbi.nlm.nih.gov/pubmed/34336124
http://dx.doi.org/10.1155/2021/9949697
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author An, Lingyue
Wu, Weizhou
Li, Shujue
Lai, Yongchang
Chen, Dong
He, Zhican
Chang, Zhenglin
Xu, Peng
Huang, Yapeng
Lei, Min
Jiang, Zheng
Zeng, Tao
Sun, Xinyuan
Sun, Xuan
Duan, Xiaolu
Wu, Wenqi
author_facet An, Lingyue
Wu, Weizhou
Li, Shujue
Lai, Yongchang
Chen, Dong
He, Zhican
Chang, Zhenglin
Xu, Peng
Huang, Yapeng
Lei, Min
Jiang, Zheng
Zeng, Tao
Sun, Xinyuan
Sun, Xuan
Duan, Xiaolu
Wu, Wenqi
author_sort An, Lingyue
collection PubMed
description Escherichia coli (E. coli) is closely associated with the formation of kidney stones. However, the role of E. coli in CaOx stone formation is not well understood. We explored whether E. coli facilitate CaOx stone formation and its mechanism. Stone and urine cultures were reviewed from kidney stone formers. The ability of calcium oxalate monohydrate (COM) aggregation was detected to evaluate the influence of uropathogenic E. coli, then gel electrophoresis and nanoLC-MS/MS to detect the crystal-adhered protein. Flagellin (Flic) and polyphosphate kinase 1 (PPK1) were screened out following detection of their role on crystal aggregation, oxidative injury, and inflammation of HK-2 cell in vitro. By transurethral injection of wild-type, Ppk1 mutant and Flic mutant strains of E. coli and intraperitoneally injected with glyoxylate in C57BL/6J female mice to establish an animal model. We found that E. coli was the most common bacterial species in patients with CaOx stone. It could enhance CaOx crystal aggregation both in vitro and in vivo. Flagellin was identified as the key molecules regulated by PPK1, and both of them could facilitate the crystal aggregation and mediated HK-2 cell oxidative injury and activated the inflammation-related NF-κB/P38 signaling pathway. Wild-type strain of E. coli injection significantly increased CaOx deposition and enhanced oxidative injury and inflammation-related protein expression, and this effect could be reversed by Ppk1 or Flic mutation. In conclusion, E. coli promotes CaOx stone formation via enhancing oxidative injury and inflammation regulated by the PPK1/flagellin, which activated NF-κB/P38 pathways, providing new potential drug targets for the renal CaOx calculus precaution and treatment.
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spelling pubmed-82920732021-07-31 Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation An, Lingyue Wu, Weizhou Li, Shujue Lai, Yongchang Chen, Dong He, Zhican Chang, Zhenglin Xu, Peng Huang, Yapeng Lei, Min Jiang, Zheng Zeng, Tao Sun, Xinyuan Sun, Xuan Duan, Xiaolu Wu, Wenqi Oxid Med Cell Longev Research Article Escherichia coli (E. coli) is closely associated with the formation of kidney stones. However, the role of E. coli in CaOx stone formation is not well understood. We explored whether E. coli facilitate CaOx stone formation and its mechanism. Stone and urine cultures were reviewed from kidney stone formers. The ability of calcium oxalate monohydrate (COM) aggregation was detected to evaluate the influence of uropathogenic E. coli, then gel electrophoresis and nanoLC-MS/MS to detect the crystal-adhered protein. Flagellin (Flic) and polyphosphate kinase 1 (PPK1) were screened out following detection of their role on crystal aggregation, oxidative injury, and inflammation of HK-2 cell in vitro. By transurethral injection of wild-type, Ppk1 mutant and Flic mutant strains of E. coli and intraperitoneally injected with glyoxylate in C57BL/6J female mice to establish an animal model. We found that E. coli was the most common bacterial species in patients with CaOx stone. It could enhance CaOx crystal aggregation both in vitro and in vivo. Flagellin was identified as the key molecules regulated by PPK1, and both of them could facilitate the crystal aggregation and mediated HK-2 cell oxidative injury and activated the inflammation-related NF-κB/P38 signaling pathway. Wild-type strain of E. coli injection significantly increased CaOx deposition and enhanced oxidative injury and inflammation-related protein expression, and this effect could be reversed by Ppk1 or Flic mutation. In conclusion, E. coli promotes CaOx stone formation via enhancing oxidative injury and inflammation regulated by the PPK1/flagellin, which activated NF-κB/P38 pathways, providing new potential drug targets for the renal CaOx calculus precaution and treatment. Hindawi 2021-07-13 /pmc/articles/PMC8292073/ /pubmed/34336124 http://dx.doi.org/10.1155/2021/9949697 Text en Copyright © 2021 Lingyue An et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
An, Lingyue
Wu, Weizhou
Li, Shujue
Lai, Yongchang
Chen, Dong
He, Zhican
Chang, Zhenglin
Xu, Peng
Huang, Yapeng
Lei, Min
Jiang, Zheng
Zeng, Tao
Sun, Xinyuan
Sun, Xuan
Duan, Xiaolu
Wu, Wenqi
Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation
title Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation
title_full Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation
title_fullStr Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation
title_full_unstemmed Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation
title_short Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation
title_sort escherichia coli aggravates calcium oxalate stone formation via ppk1/flagellin-mediated renal oxidative injury and inflammation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292073/
https://www.ncbi.nlm.nih.gov/pubmed/34336124
http://dx.doi.org/10.1155/2021/9949697
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