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

Abstract

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.

• Authors: Lingyue An, Weizhou Wu, Shujue Li, Yongchang Lai, Dong Chen, Zhican He, Zhenglin Chang, Peng Xu, Yapeng Huang, Min Lei, Zheng Jiang, Tao Zeng, Xinyuan Sun, Xuan Sun, Xiaolu Duan, Wenqi Wu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 9949697 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34336124 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Lingyue An et al.

Chemical References

• Flagellin
• Calcium Oxalate

Topics

• Animals
• Calcium Oxalate (chemistry)
• Disease Models, Animal
• Escherichia coli (pathogenicity)
• Female
• Flagellin
• Humans
• Inflammation (physiopathology)
• Kidney (pathology)
• Kidney Calculi (pathology)
• Mice
• Oxidative Stress (physiology)
• Signal Transduction