12-O-tetradecanoylphorbol-13-acetate induces selective desquamation of superficial cells in rat urinary bladder epithelium

Abstract

12-O-tetradecanoylphorbol-13-acetate (TPA) is known to affect the proliferation and/or differentiation of several types of cells. We injected TPA directly into the lumen of rat bladder to determine, using scanning and transmission electron microscopy, its effects on the bladder epithelium in vivo. At 1 h after TPA injection (1 microgram/ml), the superficial cells of the epithelium had changed their morphology, and large spherical vacuoles occupied their cytoplasm. In some areas, the underlying intermediate cells were exposed by the desquamation of the superficial cells. During the next few hours, TPA was excreted from the bladder lumen by voluntary micturition, but the desquamation of the superficial cells proceeded further. All the superficial cells were lost from the luminal surface by 24 h after TPA injection. The changes noted were specific for the superficial cells and were not observed in the intermediate or basal cells. After 24 h, part of the epithelium had a three-layer structure, indicating that regeneration was taking place. These results demonstrate that TPA selectively affects and desquamates superficial cells in a short period of time. This experimental system may be useful for studying in vivo cell proliferation and/or differentiation.

Rapid differentiation of superficial urothelial cells after chitosan-induced desquamation

“…Several in vivo and in vitro models have thus been applied to study the differentiation process of urothelial cells. In in vivo studies, mainly cyclophosphamide Veranic et al2004), 12-o-tetradecanoylphorbol-13-acetate (TPA) (Watanabe and Sasaki 1992), sodium saccharin (Romih et al 1998) or hyperthermic shock (Jacob et al 1982) have been used to remove urothelial cells from the bladder and the renewal process has then been sequentially studied. Most procedures that efficiently induce cell removal resulted in an inflammatory response, prolonged cell desquamation and caused hyperplasia of the urothelium, all of which disturbs the process of normal differentiation.…”

Repeated treatments with chitosan in combination with antibiotics completely eradicate uropathogenic Escherichia coli from infected mouse urinary bladders

“…However, after injury, the proliferation and differentiation of basal cells increase rapidly, leading to the fast renewal of intermediate and superficial cells and the reestablishment of the permeability barrier function [3,12]. Several experimental methods for inducing urothelial injury have been developed as means to compromise and study the barrier function [16][17][18][19][20][21]. The intravesical application of the biopolymer chitosan serves as an easily controlled method to detach the superficial layer of urothelial cells [22].…”

The Use of Polymer Chitosan in Intravesical Treatment of Urinary Bladder Cancer and Infections

“…To improve the penetration of drugs into urothelial tissue, several inducers of urothelial cell desquamation could be applied. Among them, mainly cyclophosphamide [12,17], 12-o-tetradecanoylphorbol-13-acetate (TPA) [18], sodium saccharin [19], or hyperthermic shock [20] have been used to largely remove urothelial cells. Most procedures that induced cell removal resulted in an inflammatory response, prolonged cell desquamation, and transitional hyperplasia of the urothelium.…”