Abstract
Purpose: Recent data from the literature and the experimental work of the authors clearly indicate that TGF- beta 1 is a key modulator of cellular events, for example, induction of terminal differentiation, resulting in radiation-induced fibrosis. Therefore, the present study analysed which cellular processes induced by exogeneously added TGF- beta could be responsible for the induction, development and manifestation of the fibrotic phenotype in culture. Materials and methods: Rat lung fibroblast cultures (passage 1) were used. As a function of treatment with TGF- beta and/or anti-TGF beta -antibody, the clonogenic activity and differentiation pattern were analysed by colony-formation assays. Results: It could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF- beta 1 resulted in a pronounced shift in the differentiation pattern, i.e. induction of post-mitotic fibrocytes. This TGF- beta 1-dependent terminal differentiation could be abolished by simultaneous treatment with a neutralizing antibody directed against TGF- beta 1. Conclusions: The data presented indicate that TGF- beta 1 is one major candidate mediating the accelerated terminal differentiation of progenitor fibroblasts to post-mitotic functional fibrocytes, which results in the fibrotic phenotype of this cell system.
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