Bladder filling and voiding affect umbrella cell tight junction organization and function

Abstract

Epithelial cells are continuously exposed to mechanical forces including shear stress and stretch, although the effect these forces have on tight junction (TJ) organization and function are poorly understood. Umbrella cells form the outermost layer of the stratified uroepithelium and undergo large cell shape and surface area changes during the bladder cycle. Here we investigated the effects of bladder filling and voiding on the umbrella cell TJ. We found that bladder filling promoted a significant increase in the length of the TJ ring, which was quickly reversed within 5 min of voiding. Interestingly, when isolated uroepithelial tissue was mounted in Ussing chambers and exposed to physiological stretch, we observed a 10-fold drop in both transepithelial electrical resistance (TER) and the umbrella cell junctional resistance. The effects of stretch on TER were reversible and dependent on the applied force. Furthermore, the integrity of the umbrella cell TJ was maintained in the stretched uroepithelium, as suggested by the limited permeability of biotin, fluorescein, and ruthenium red. Finally, we found that depletion of extracellular Ca(2+) by EGTA completely disrupted the TER of unstretched, but not of stretched uroepithelium. Taken together, our studies indicate that the umbrella cell TJ undergoes major structural and functional reorganization during the bladder cycle. The impact of these changes on bladder function is discussed.

Revealing the molecular mechanism of colorectal cancer by establishing LGALS3-related protein-protein interaction network and identifying signaling pathways

“…Claudins, major components of the strands, promote cell-cell adhesion (31). CLDN8 codes for tight junction proteins expressed in distal nephron epithelium, and it is considered a candidate marker for distinguishing chromophobe renal cell carcinoma from other types of renal cancer (32).…”

Mathematical modelling of stretch-induced membrane traffic in bladder umbrella cells

“…Intermediate cells are marked with yellow asterisks, and basal cells with white asterisks. Reproduced with permission (Carattino et al, 2013). (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.…”

Future Perspectives in Bladder Tissue Engineering

“…Its regenerative capability stems from a muti-layered structure, whereby the most mature cells lining the bladder are shed and replaced by younger cells in the deeper layers. This stratification also facilitates maintenance of the blood-urine barrier as the bladder stretches during filling [1]. Additionally, the urothelium contains cells which transduce bladder sensations, including irritation, distention, and pain [10].…”

“…The urothelium serves as an impenetrable barrier providing urine containment [1]. The lamina propria houses vasculature that provides essential oxygen and nutrients to the urothelium, while anchoring it to the bladder muscle [2].…”