Persistent Escherichia coli infection in renal tubular cells enhances calcium oxalate crystal–cell adhesion by inducing ezrin translocation to apical membranes via Rho/ROCK pathway
Issued Date
2022-07-01
Resource Type
ISSN
1420682X
eISSN
14209071
Scopus ID
2-s2.0-85132999070
Pubmed ID
35751006
Journal Title
Cellular and Molecular Life Sciences
Volume
79
Issue
7
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cellular and Molecular Life Sciences Vol.79 No.7 (2022)
Suggested Citation
Kanlaya R., Thongboonkerd V. Persistent Escherichia coli infection in renal tubular cells enhances calcium oxalate crystal–cell adhesion by inducing ezrin translocation to apical membranes via Rho/ROCK pathway. Cellular and Molecular Life Sciences Vol.79 No.7 (2022). doi:10.1007/s00018-022-04414-y Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83686
Title
Persistent Escherichia coli infection in renal tubular cells enhances calcium oxalate crystal–cell adhesion by inducing ezrin translocation to apical membranes via Rho/ROCK pathway
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
Recent evidence has suggested that recurrent urinary tract infection (UTI) can cause not only infection stones but also metabolic stones (e.g., those containing calcium oxalate monohydrate or COM). However, precise mechanisms underlying UTI-induced metabolic stones remained unknown. In this study, Escherichia coli, the most common bacterium found in recurrent UTI was used to establish the in vitro model for persistent infection of renal epithelial cells. The promoting effects of persistent E. coli infection on kidney stone formation were validated by COM crystal–cell adhesion assay, followed by immunofluorescence study for changes in surface expression of the known COM crystal receptors. Among the five receptors examined, only ezrin had significantly increased level on the surface of persistently infected cells without change in its total level. Such translocation of ezrin to apical membranes was confirmed by Western blotting of apical membrane and cytosolic fractions and confocal microscopic examination. Additionally, persistent infection increased phosphorylation (Thr567) of ezrin. However, all of these changes induced by persistent E. coli infection were significantly inhibited by small-interfering RNA (siRNA) specific for ezrin or a Rho-associated kinase (ROCK)-specific inhibitor (Y-27632). In summary, this study provides a piece of evidence demonstrating that persistent infection by E. coli, one of the non-urease-producing bacteria, may contribute to COM metabolic stone formation by translocation of ezrin to apical membranes, thereby promoting COM crystal–cell adhesion. Such ezrin translocation was mediated via Rho/ROCK signaling pathway. These findings may, at least in part, explain the pathogenic mechanisms underlying recurrent UTI-induced metabolic kidney stone disease. Graphical abstract: [Figure not available: see fulltext.].