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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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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. |
format | Online Article Text |
id | pubmed-8292073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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