Deficits of urothelial cell proliferation, cytoskeleton, and barrier function protein expressions in patients with recurrent and persistent urinary tract infections.

ABSTRACT

OBJECTIVES: Recurrent urinary tract infection (rUTI) is a common infectious disease in women. This study investigated the urothelial cell proliferation, the cytoskeleton, barrier proteins, and inflammatory protein expression in women with rUTIs. METHODS: Female patients with recurrent or persistent UTIs were recruited. Bladder mucosal specimens were investigated by Western blot and immunohistochemical staining for the urothelial cytoskeleton proteins cytokeratin 5 (CK5), CK14, and CK20; proteins involved in cellular proliferation, including CD34, sonic hedgehog (SHH), and tumor protein 63 (TP63); barrier proteins zonula occludens 1 (ZO-1) and E-cadherin; inflammatory proteins p38 and tryptase; and proapoptotic proteins Bcl2-associated agonist of cell death protein (BAD), Bcl2-associated X protein (BAX), and caspase-3. Women with stress urinary incontinence without bladder symptoms served as controls. Bladder specimens from 18 recurrent UTI patients with rUTIs and 12 persistent UTIs, and 17 controls were analyzed, and protein expressions were compared between the three groups. RESULTS: Cell proliferation protein expression for CD34, SHH, and TP63 was significantly lower in the urothelium of patients with rUTIs than in controls. Expression of CK5 increased, whereas CK20 decreased significantly in rUTIs compared with those of controls. Apoptotic proteins BAD, BAX, and caspase-3 were significantly higher in patients with rUTIs. However, barrier proteins ZO-1 and E-cadherin, and tryptase were not significantly lower in patients with rUTIs. CONCLUSION: Deficits in expression of proteins involved in urothelial cell proliferation, cytoskeleton, and barrier function were noted in patients with rUTIs. These urothelial deficits may be due to deficient proliferation and differentiation resulting in inadequate urothelial barrier function and further in rUTIs.