Inflammation and Barrier Function Deficits in the Bladder Urothelium of Patients with Chronic Spinal Cord Injury and Recurrent Urinary Tract Infections

Abstract

Patients with spinal cord injury (SCI) commonly experience neurogenic voiding dysfunctions and urinary tract complications, including recurrent urinary tract infections (rUTI). The bladder mucosa barrier function contributes to UTI prevention. This study investigated changes in bladder urothelium protein expression in patients with SCI and rUTI. From June 2011 to November 2017, 23 patients (19 men and 4 women) with chronic SCI were enrolled (mean age: 43 years. Bladder tissues from 6 healthy adults served as the normal control group. Biopsy samples (9 partial cystectomies and 14 bladder biopsies) were analyzed for functional biomarkers using western blot and immunohistochemistry analysis. The barrier function proteins E-cadherin, zonula occludens 1 (ZO-1) and uroplakin III (UPK-3) were significantly reduced, whereas tumor protein p63 (TP63) was significantly increased in SCI patients compared with controls. No significant differences in basal cell progenitor proteins were observed between groups. The proliferation marker Ki-67, the proapoptotic marker BCL-2-associated X protein (BAX), and proinflammatory proteins were increased in patients with SCI compared with controls. No significant differences were observed between SCI patients with and without recently rUTI. These results suggest that SCI patients experience chronic bladder inflammation, increased apoptosis, and reduced barrier function, contributing to rUTI.