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. 2022 Jan 20;10(2):220.
doi: 10.3390/biomedicines10020220.

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

Shu-Yu Wu  1   2 , Yuan-Hong Jiang  2   3 , Jia-Fong Jhang  2   3 , Yung-Hsiang Hsu  4   5 , Han-Chen Ho  6 , Hann-Chorng Kuo  2   3
Affiliations

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

Shu-Yu Wu et al. Biomedicines. .

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.

Keywords: recurrent urinary tract infection; regenerative deficits; spinal cord injury; urothelial dysfunction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemistry showing barrier and junction proteins E-cadherin and uroplakin-III (UPK-3) in bladder tissues from chronic spinal cord injury (SCI) patients and control subjects. E-cadherin and UPK-3 are positive (brown) in superficial umbrella cells in control group but lack in SCI bladder. Labeling of lamina propria is unspecific. L, lumen; UC, umbrella cell; LP, lamina propria. Scale bars: 20 μm.
Figure 2
Figure 2
Immunohistochemistry showing proliferation protein Ki-67 and pro-apoptosis proteins (BAX) in bladder tissues of chronic spinal cord injury (SCI) patients and control subjects. Index of Ki67 is lower, making it difficult to identified differences with human eyes. BAX is positive in superficial umbrella cells in SCI group. Labeling of lamina propria is unspecific. L, lumen; UC, umbrella cell; LP, lamina propria. Scale bars: 20 μm.
Figure 3
Figure 3
Immunohistochemistry showing inflammation proteins tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in bladder tissues of chronic SCI patients and control subjects. TNF-α and TGF-β are more obvious in SCI group than control group. Labeling of lamina propria is unspecific. L, lumen; UC, umbrella cell; LP, lamina propria. Scale bars: 20 μm.
Figure 4
Figure 4
Possible pathway of bladder mucosa injury after chronic SCI.
See this image and copyright information in PMC

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