Characterization of distinct functions for growth factors in murine transitional epithelial cells in primary organotypic culture.

Although previous studies indicate that growth factors can affect several physiological processes in epithelia, their role in the biological dynamics of transitional epithelium of the bladder is not yet established. This study investigates the functional consequences of a direct action of EGF, TGF beta, FGF-1, FGF-2, PDGF-AA, and PDGF-BB on mouse urothelium in organoid-like primary cultures. Confluent and nonconfluent cultures served as a model for intact and regenerating urothelium, respectively. EGF and FGF-1 stimulated in both models under serum-free conditions the BrdU and [3H]-thymidine incorporation. This resulted in an increase in the number of cell layers, but the cultures assumed a less organoid-like morphology. In addition, EGF and FGF-1 stimulated the expansion of nonconfluent cultures. TGF beta inhibited proliferation, caused a decrease in the number of cell layers, and blocked expansion. Moreover, TGF beta induced the terminal differentiation and apoptosis of urothelial cells. In nonconfluent cultures PDGF-BB slightly stimulated the increase in the outgrowth area, but no other effect on the parameters for proliferation and differentiation was observed. FGF-2 and PDGF-AA did not affect any of the studied parameters. These data are consistent with the hypothesis that EGF and FGF-1 can promote wound healing and/or hyperplasia through direct action on the epithelial cells, while TGF beta promotes the development of a normal, differentiated transitional epithelium.