Escherichia coli infection induces mucosal damage and expression of proteins promoting urinary stone formation

Abstract

The effect of urinary tract infection (UTI) on mucosal damage and production of proteins promoting urinary stone formation has not been elucidated. Osteopontin production, with associated mucosal damage due to UTI, may allow easier crystal retention and nucleation resulting in stone formation. The aim of this study is to demonstrate that expression of osteopontin (OPN), OPN mRNA, TLR-4, JNK, TNFR-1, iNOS, HMGB-1, and apoptosis process is higher than normal at renal tubular cells due to urinary tract infection by Escherichia coli. Adult male New Zealand strain rabbits were used. Thirty New Zealand strain rabbits were divided into three groups. The first group acted as controls, the second group underwent ligation of right ureter, and the third group underwent ligation of right ureter and injection of Escherichia coli 105/ml proximal to ligation. Nephrectomy and histological examination were performed after 5 days. All groups were HE stained to examine mucosal damage, specific monoclonal antibodies for TLR-4, JNK, mRNA OPN, OPN, TNFR-1, iNOS and HMGB-1. Apoptotic nuclei were demonstrated using TUNEL method. Statistical calculations were performed using ANOVA test, with p < 0.05 considered significant. The findings confirmed the hypothesis that infection of urinary tract by Escherichia coli demonstrated higher expression of OPN, OPN mRNA, TLR-4, JNK, TNFR-1, iNOS, HMGB-1, apoptosis process and mucosal damage than normal. Infection of urinary tract by Escherichia coli caused higher than normal expression of promoter protein osteopontin and mucosal damage at renal tubular cells. These suggest that urinary infection may promote stone formation by mucosal damage and elevate promoter protein osteopontin at tubulus cell, allowing easier crystal retention and nucleation.

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

“…Weak inflammation was observed in the △PPK1-CFT073 and △Flic-CFT073 groups. This may be related to other virulence factors secreted by E. coli, which are less influenced by PPK1 (like LPS) [43,44]. However, the results of us supported LPS may not a leading element in the aggregation of CaOx crystals, which is also consistent with Rattiyaporn's study [34].…”

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

“…Another possibility is that bacteria may alter urine supersaturation via production of citrate lyase, which decreases the urine citrate levels and lead to crystal formation [19]. Lastly, bacteria may induce an inflammatory response and the release of proinflammatory proteins, which form the stone matrix inner core and progress from crystal to stone [20].…”

Transcriptional alterations in bladder epithelial cells in response to infection with different morphological states of uropathogenic Escherichia coli

“…HMGB1 has many functions in the cell, including a proinflammatory role when released into the extracellular environment by passive release from necrotic cells or in an active manner following cell stimulation with e.g., LPS, IL-1β and TNF-α 30 . In the urinary tract, HMGB1 has been mainly been associated with the progression of urothelial carcinoma 31 , but bacterial infection of the urinary tract also stimulates increased expression of HMGB1 32 . Besides its own direct intracellular signaling pathway, TREM1 activation cross-talks with intracellular signalling pathways of several TLRs and can thereby contribute to and amplify the magnitude of inflammation 33 .…”