MOLECULAR AND CELLULAR BASIS OF RADIATION FIBROSIS

Purpose: Recent data from the literature and the experimental work of the authors clearly indicate that TGF-beta 1 is a key modulator of cel lular events, for example, induction of terminal differentiation, resu lting in radiation-induced fibrosis. Therefore, the present study anal ysed which cellular processes induced by exogeneously added TGF-beta c ould be responsible for the induction, development and manifestation o f the fibrotic phenotype in culture. Materials and methods: Rat lung f ibroblast cultures (passage 1) were used. As a function of treatment w ith TGF-beta and/or anti-TGF-beta-antibody, the clonogenic activity an d differentiation pattern were analysed by colony-formation assays. Re sults: It could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF-beta 1 resulted in a pronounced shift in the diff erentiation pattern, i.e. induction of post-mitotic fibrocytes. This T GF-beta 1-dependent terminal differentiation could be abolished by sim ultaneous treatment with a neutralizing antibody directed against TGF- beta 1. Conclusions: The data presented indicate that TGF-beta 1 is on e major candidate mediating the accelerated terminal differentiation o f progenitor fibroblasts to post-mitotic functional fibrocytes, which results in the fibrotic phenotype of this cell system.