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 express ion of growth factors and their receptors by in situ hybridization and immunocytochemistry during regeneration after acute injury of mouse u rothelium in vivo. These data were correlated with changes in morpholo gy and proliferation during regeneration. Except for an enhanced muscu lar transforming growth factor-beta(1) (TGF-beta(1)) and TGF-beta type II receptor expression, changes in expression patterns of growth fact ors or receptors were confined to the urothelium. Increased mucosal RN A expression of insulin-like growth factor-II (IGF-II) and particularl y of type I IGF receptor, as well fibroblast growth factor-1 (FGF-1) b ut not of FGF-2, coincided with re-epithelialization and urothelial pr oliferation. Both high levels of urothelial TGF-beta(1) RNA and protei n expression were associated with re-epithelialization and differentia tion. In addition, TGF beta type II receptor protein expression was si milarly 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 wi th the notion that urothelial regeneration can be achieved by paracrin e or autocrine acting, urothelium-derived growth factors. Since analog ous growth factor RNA expression patterns in regenerating skin epiderm is have been found, a more general growth factor-regulated mechanism f or epithelial regeneration may be suggested.