Expression of growth factors and receptors during specific phases in regenerating urothelium after acute injury in vivo.

We investigated the spatio-temporal changes in RNA and protein expression of growth factors and their receptors by in situ hybridization and immunocytochemistry during regeneration after acute injury of mouse urothelium in vivo. These data were correlated with changes in morphology and proliferation during regeneration. Except for an enhanced muscular transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta type II receptor expression, changes in expression patterns of growth factors or receptors were confined to the urothelium. Increased mucosal RNA expression of insulin-like growth factor-II (IGF-II) and particularly of type I IGF receptor, as well as fibroblast growth factor-1 (FGF-1) but not of FGF-2, coincided with re-epithelialization and urothelial proliferation. Both high levels of urothelial TGF-beta 1 RNA and protein expression were associated with re-epithelialization and differentiation. In addition, TGF beta type II receptor protein expression was similarly enhanced in the same urothelial cells. Platelet-derived growth factor-A (PDGF-A) RNA was expressed constitutively in the mucosa but decreased in the reepithelialization phase. The data are consistent with the notion that urothelial regeneration can be achieved by paracrine or autocrine acting, urothelium-derived growth factors. Since analogous growth factor RNA expression patterns in regenerating skin epidermis have been found, a more general growth factor-regulated mechanism for epithelial regeneration may be suggested.