Uroplakins and cytokeratins in the regenerating rat urothelium after sodium saccharin treatment

Abstract

A sodium saccharin (NaSac) diet was used to induce cell damage and regeneration in the urothelium of the male rat urinary bladder. Foci of terminally differentiated superficial cell exfoliation were detected after 5 weeks and their number increased after 10 and 15 weeks of the diet. At the sites of superficial cell loss, regenerative simple hyperplasia developed. Within 5 weeks of NaSac removal, regeneration re-established normal differentiated urothelium. In order to follow urothelial differentiation during regeneration we studied the expression of uroplakins and cytokeratins by means of immunocytochemistry and immunohistochemistry, respectively. Normal urothelium was characterised by terminally differentiated superficial cells which expressed uroplakins in their luminal plasma membrane and cytokeratin 20 (CK20) in the cytoplasm. Basal and intermediate cells were CK20 negative and cytokeratin 17 (CK17) positive. In hyperplastic urothelium all cells synthesised CK17, but not CK20. Differentiation of the superficial layer was reflected in three successive cell types: cells with microvilli, cells with rounded microridges and those with a rigid-looking plasma membrane on the luminal surface. The cells with microvilli did not stain with anti-uroplakin antibody. When the synthesis of uroplakins was detected rounded microridges were formed. With the elevated expression of uroplakins the luminal plasma membrane becomes rigid-looking which is characteristic of asymmetric unit membrane of terminally differentiated cells. During differentiation, synthesis of CK17 ceased in superficial cells while the synthesis of CK20 started. These results indicate that during urothelial regeneration after NaSac treatment, specific superficial cell types develop in which the switch to uroplakin synthesis and transition from CK17 to CK20 synthesis are crucial events for terminal differentiation.

Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding

“…The apical membranes of the umbrella cells were obviously TRPV4 negative, while the basolateral membranes seem to carry at least some TRPV4 (Figure 2, A and B) (31,32). No differences in microscopic structural (based on immunohistochemistry) and ultrastructural (based on electron microscopy) differences were found between bladders from both groups (data not shown).…”

Bladder tissue formation from cultured bladder urothelium

“…The urothelial cells had a transitional cell phenotype with expression of uroplakins, illustrating the full maturity of the recombinant urothelium. Investigators have shown that immature urothelium does not express uroplakin (Romih et al, 1998;Lavelle et al, 2002). In addition, a sub-epithelial connective tissue layer surrounded urothelial cell clusters, mimicking a lamina propria layer that exists in native bladders.…”

Relationship of Cytokeratin 20 and CD44 Protein Expression with WHO/ISUP Grade in pTa and pT1 Papillary Urothelial Neoplasia

“…The regeneration of urothelium after urothelial damage is accompanied by changes in protein synthesis related to differentiation by mechanisms that have not yet been established (47). This transition from basal to terminally differentiated superficial cells in the urothelium is reflected in the morphological and antigenic characteristic of each layer.…”