Activities of Ca²⁺-related ion channels during the formation of kidney stones in an infection-induced urolithiasis rat model

Abstract

Bacterial infection has long been recognized to contribute to struvite urinary stone deposition; however, its contribution to the development of chronic kidney stones has not been extensively investigated. In the present study, we hypothesized another possible method of bacteria contributing to the formation of calcium oxalate (CaOx) that accounts for the biggest part of the kidney stone. Bacteria may play important roles by influencing renal Ca2+-related ion channel activities, resulting in chronic inflammation of the kidney along with rapid aggregation of stones. We examined the correlation among infection-promoted CaOx kidney stones and alterations in Ca2+-related ion channels in an animal model with experimentally induced Proteus mirabilis and foreign body infection. After the bladder was infected for 7 days, the data demonstrated that stones were presented and induced severe renal tubular breakage as well as altered levels of monocyte chemoattractant protein-1, cyclooxygenase-2, osteopontin, and transient receptor potential vanilloid member 5 expression, reflecting responses of kidney ion channels. Monocyte chemoattractant protein-1, osteopontin, and transient receptor potential vanilloid member 5 expression was significantly downregulated over time, indicating the chronic inflammation phase of the kidney and accelerated aggregation of CaOx crystals, respectively, whereas cyclooxygenase-2 exhibited no differences. These results indicated that bacterial infection is considerably correlated with an alteration in renal Ca2+-related ion channels and might support specific and targeted Ca2+-related ion channel-based therapeutics for urolithiasis and related inflammatory renal damage.

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

“…It has been reported that MCP-1, expressed in normal renal epithelial cells, is one of the key factors involved in the regulation of the inflammatory response [40]. It can be upregulated by stimulation of CaOx crystals and participates in CaOxinduced renal inflammation [41]. Our results showed that E. coli-induced inflammation was decreased after knockout of Ppk1 and Flic in vitro and in vivo.…”

Profiling the urinary microbiome in men with calcium-based kidney stones

“…Among these pathways, ion channels are key regulators of the cell membrane and have been demonstrated as an entrance gate in bacteria-host interactions [28]. In an infection-induced urolithiasis rat model, the activities of calcium related ion channels were reported to be influenced by bacterial infection, and correlated with chronic inflammation of the kidney along with rapid aggregation of stones [29]. Moreover, transient receptor potential vanilloid 5 (TRPV5), a member of the transient receptor potential family of ion channels, has also been proved to be closely associated with urinary stone formation [30].…”

Association of Kidney Stones and Recurrent UTIs: the Chicken and Egg Situation. A Systematic Review of Literature

“…Additional molecular mechanisms have been studied to comprehend crystal aggregation and stone growth. It has been hypothesized that bacterial polysaccharides of the genus Proteus , macromolecules that contain negatively charged residues and are able to bind Ca(2 +) and Mg(2 +), might lead to the accumulation of these ions around bacterial cells and accelerate the crystallization process [ 36 , 37 ]. An in vitro model was used to study intracellular growth and crystallization in the presence of bacterial strains of P. mirabilis , Klebsiella pneumoniae , and Escherichia coli [ 38 ].…”