BERKELEY, CA (UroToday.com) - Previous reports have suggested that the bladder epithelia barrier may be compromised in PBS/IC. Antiproliferative factor is a small glycoprotein made specifically by bladder epithelial cells in patients with PBS/IC that induces changes in expression of certain epithelial cell proteins and profoundly inhibits cell growth. Zhang and colleagues sought to determine whether APF might be involved in the regulation of bladder epithelial paracellular barrier function by testing its effects on radiolabeled inulin and mannitol flux in normal bladder epithelial cell monolayers shown to express zonula occludens-1 and occludin proteins, a part of the apical tight junction complex.

APF treatment caused significant increases in the paracellular permeability of normal bladder epithelial cell monolayers and the attenuation of tight junctions compared to mock APF, similar to changes seen in IC cells. APF treatment also decreased expression of the tight junction proteins zonula occludens-1 and occludin.

The authors note that whether increased permeability of the bladder epithelial barrier caused by APF or another agent is directly or indirectly related to the pathophysiology of PBS/IC is currently unproven. However, increased exposure of submucosal cells, including afferent neurons, to urinary metabolites as a result of increased epithelial permeability could conceivably result in irritative voiding symptoms, as demonstrated in rodent models of cystitis, in which the bladder epithelial barrier was compromised by treatment with protamine sulfate or cyclophosphamide. Males with chronic pelvic pain who are APF positive seem to have irritative voiding symptoms in addition to their pain, suggesting the importance of the finding.

J Urol. 2005 December; 174:2382-2387