Loss of 15-hydroxyprostaglandin dehydrogenase expression disrupts urothelial differentiation.

OBJECTIVES: Urothelial differentiation is essential for the maintenance of urinary bladder function. We explored the expression and function of 15-hydroxyprostaglandin dehydrogenase (PGDH) during urothelial differentiation.
METHODS: We evaluated expression of PGDH by Northern and Western blotting and immunostaining in human urothelial cultures, cell lines, and tissues. We determined enzymatic function using enzyme-linked immunosorbent assay. Small inhibitory ribonucleic acids were used to inhibit PGDH expression in human bladder cancer cells.
RESULTS: We found PGDH messenger ribonucleic acid was increased in an in vitro model of human urothelial differentiation by Northern blotting. Western blotting of human bladder cancer cell lines showed expression in the well-differentiated RT4 cells and no expression in poorly differentiated UC3 cells. Immunostaining showed that PGDH expression increased with differentiation in normal bladder urothelium. The enzyme was functional in the well-differentiated RT4 human bladder cancer cell line. Inhibition of PGDH expression resulted in disruption of E-cadherin expression at cell-cell contacts in well-differentiated RT4 bladder cancer cells.
CONCLUSIONS: These studies indicate that PGDH expression is associated with urothelial differentiation, and loss of PGDH expression results in disruption of urothelial differentiation.