|Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Mammalian urinary bladder epithelium is composed of three cell layrs, basal, intermediate and superficial ones. In normal conditions, this epithelium is very stable and the epithelial cells seldom proliferate. By the instillation of 12-O-tetradecanoylphorbol-13-acetate (TPA) into the bladder, most of the superficial cells were desquamated and then the epithelial cells proliferated reconstructing the epithelium. In rats, basal cells proliferated at 18-24 hr after TPA instillation, and epithelial regeneration completed within about 8 days. In mice, however, the proliferation occurred in intermediate cells and lasted in several days.
The effect of urinary EGF on cell proliferation in the TPA-treated urothelium was studied by injecting anti-EGF receptor antibody into the bladder to block the receptor activety.However, the cell proliferation was not changed by the treatment. And further, immunohistochemistry did not show the specific expression of EGF receptor in rats and mice urothelium. From these results, EGF in urine may not be important for the cell proliferation in the urothelial regeneration.
To know precise position of the proliferating cells in urothelium, the contact between the basement membrane and each of the cells in the three cell layrs was studied. By the instillation of horseradish peroxidase (HRP) into the lumen, superficial cells were labeled selectively with HRP and their whole cytoplasm was visualized with DAB reactions.According to light and electron microscopy, all superficial cells did not attached to the basement membrane, which indicated that the urothelium was not the "pseudostratified" but "multilayred" epithelium. This HRP uptake by superficial cells may be a new function of the urothelial cells. The relation between the intermediate cells and the basement membrane was not confirmed as yet, so the precise difference in cell proliferation mechanisms in rats and mice was not clear.